JP2022096766A - Cell transplantation apparatus, unit for housing cell, method for housing transplant, and transplant arrangement method - Google Patents

Abstract

To provide a cell transplantation apparatus capable of controlling arrangement of a cell group in a tissue of a transplant destination, a unit for housing cells, a method for housing transplants, and a transplant arrangement method.SOLUTION: A cell transplantation apparatus 100 includes: a needle-like part 10 extending cylindrically and having an opening 11 at an end part of the needle-like part 10; and a rod-like body 30 extending inward of the needle-like part 10 along the direction where the needle-like part 10 extends and having an end part capable of piercing the transplant. The rod-like body 30 is configured to be relatively movable to the needle-like part 10 between a position where an end part of the rod-like body 30 is arranged inside the needle-like part 10 and a position where the end part of the rod-like body 30 projects from the opening 11 of the needle-like part 10. The cell transplantation apparatus 100 is suitably used for transplantation of a transplant including a cell group to an organism.SELECTED DRAWING: Figure 1

Description

The present invention relates to a cell transplant device, a cell storage unit, a method for containing a transplant, and a method for arranging a transplant.

The use of technology for transplanting cell groups into living organisms is advancing. For example, attempts have been made to regenerate hair by culturing a group of cells that contribute to the formation of hair follicles, which are organs that produce hair, and transplanting the group of cells into the skin. Hair follicles are formed by the interaction of mesenchymal cells and epithelial cells. For good hair regeneration, it is desirable that the transplanted cell population yields hair follicles with normal tissue structure and good hair-forming ability. Therefore, various researches and developments have been carried out on a method for producing a cell group capable of forming such hair follicles (see, for example, Patent Documents 1 to 3).

International Publication No. 2017/073625 International Publication No. 2012/108069 Japanese Unexamined Patent Publication No. 2008-29331

In the developmental process of multicellular organisms, a large number of progenitor cells generated from stem cells recognize each other's appropriate three-dimensional positional relationship and promote differentiation, thereby forming a complex structure of each organ. That is, for normal tissue formation, it is important that the cells are arranged in an appropriate positional relationship in the process of tissue formation. On the other hand, in the above-mentioned transplantation of a cell group, a method of controlling the arrangement of the cell group in the transplant destination tissue, that is, a method of controlling the orientation of the cell group with respect to the transplant destination tissue and the positional relationship between the transplanted cells. Has not been fully considered.

For example, in order to form a normal hair follicle, two types of cell masses, that is, a cell mass of a mesenchymal cell and a cell mass of an epithelial cell, are brought into contact with each other in contact with the cell mass of the mesenchymal cell. It is necessary to place the cell mass of epithelial cells closer to the surface of the skin. However, for example, it has been difficult to control the positional relationship between the two types of cell masses inside the skin by the conventional transplantation method in which the cell group is released from the pipette to the site where the skin is incised with a scalpel.

Therefore, it is desired to develop a technique capable of controlling the arrangement of cell groups in the tissue of the transplant destination.

The cell transplantation device for solving the above-mentioned problems is a needle-shaped portion extending in a tubular shape, the needle-shaped portion having an opening at the tip portion of the needle-shaped portion, and the needle-shaped portion inside the needle-shaped portion. The rod-shaped body extending along the extending direction of the portion, comprising the rod-shaped body having a tip portion capable of piercing a transplant containing a cell group to be transplanted into a living body, and the rod-shaped body. With respect to the needle-shaped portion between the position where the tip portion of the rod-shaped body is arranged inside the needle-shaped portion and the position where the tip portion of the rod-shaped body protrudes from the opening of the needle-shaped portion. It is configured to be relatively movable.

According to the above configuration, the implant is housed in the needle-shaped portion while being pierced by the rod-shaped body. Therefore, inside the needle-shaped portion, the orientation of the transplant to the needle-shaped portion is fixed, and when the transplant contains a plurality of cell groups, the positional relationship between the cell groups is also fixed. Therefore, the implant can be placed in a predetermined orientation or positional relationship with respect to the tissue in the living body. Therefore, it is possible to control the placement of the transplant within the transplanted tissue.

In the above configuration, the tip of the rod may be sharp.
According to the above configuration, since the rod-shaped body is easily pierced by the transplanted body, the transplanted body can be smoothly accommodated in the needle-shaped portion.

In the above configuration, the outer diameter of the rod-shaped body may be 0.4 times or less the inner diameter of the needle-shaped portion.
According to the above configuration, a sufficient gap for accommodating the implant is sufficiently secured between the rod-shaped body and the inner surface of the needle-shaped portion. Therefore, it is possible to smoothly accommodate the implant in the needle-shaped portion. In addition, it is possible to suppress the load on the cell group when it is contained in the needle-shaped portion.

In the above configuration, the cell transplantation device may be provided with a mechanism for keeping the tip of the rod-shaped body protruding from the opening of the needle-shaped portion and piercing the living body.
According to the above configuration, the state in which the transplant is placed in the living body is maintained while the rod-shaped body pierces the transplant. As a result, with the passage of time, the tissue in the living body fills the circumference of the transplant. As a result, when the rod is pulled out, the implant is held down by the surrounding tissue, thus preventing the implant from moving with the rod.

In the above configuration, the cell transplantation device may include a stopper portion protruding from the rod-shaped body, and the stopper portion may have a function of suppressing the movement of the transplanted object toward the proximal end portion of the rod-shaped body.

According to the above configuration, when the rod-shaped body is moved with respect to the needle-shaped part, such as when only the needle-shaped part is pulled out from the living body, the transplant is suppressed from moving toward the base end portion of the rod-shaped body. ..
In the above configuration, at least one of the inner surface of the needle-shaped portion and the surface of the rod-shaped body may be a surface subjected to a non-adsorption treatment of cells.

According to the above configuration, the transplant is easily separated from the non-adsorbed surface. Therefore, it is possible to smoothly pull out the needle-shaped portion or the rod-shaped body when arranging the implant in the living body.

In the above configuration, the rod-shaped body has a detaching portion including the tip portion of the rod-shaped body, and the detaching portion is a state other than the detaching portion in the rod-shaped body in a state where the tip portion of the rod-shaped body is stuck in a living body. It may be configured so that it can be separated from the part of.

According to the above configuration, by separating the detached portion, the placement of the transplanted body in the living body can be completed without pulling out the rod-shaped body from the transplanted body. Therefore, the movement of the transplant is suppressed when the rod-shaped body is pulled out. The detached portion can also function as a member that induces tissue formation from the implant.

In the above configuration, the cell transplantation apparatus may include a mechanism for separating the detached portion from a portion of the rod-shaped body other than the detached portion.
According to the above configuration, the detached portion can be accurately separated.

In the above configuration, the detachment portion may be formed of a material that dissolves in the living body.
According to the above configuration, it is not necessary to remove the detached portion from the living body, so that the convenience is enhanced. Further, even if the cell transplantation device does not have a mechanism for separating the detached portion, the detached portion can be separated from the other part of the rod-shaped body.

In the above configuration, the detachment portion may have a surface coated with a substance that promotes cell attachment.
According to the above configuration, since the holding of the transplanted portion in the detached portion is stable, it is possible to prevent the transplanted portion from being displaced due to vibration or the like when the needle-shaped portion pierces the living body.

The cell accommodating unit for solving the above-mentioned problems is a cell accommodating unit provided with a cell transplanting device and a cell accommodating assisting device, and the cell transplanting device is a needle-shaped portion extending in a tubular shape and the needle. The needle-shaped portion having an opening at the tip of the shaped portion and a rod-shaped body extending along the extending direction of the needle-shaped portion inside the needle-shaped portion, and a group of cells to be transplanted into a living body. The rod-shaped body comprises the rod-shaped body having a tip portion capable of piercing the implant including The tip of the cell is configured to be relatively movable with respect to the needle-shaped portion from the position where the tip portion of the needle-shaped portion protrudes from the opening of the needle-shaped portion, and the cell storage assisting device is a holding portion extending in a tubular shape. The holding unit includes a suction unit that sucks the inside of the holding portion, and the holding portion is configured to be able to hold the cell group at the tip end portion of the holding portion by suction of the suction portion, and is configured to hold the cell group. Faces the tip of the holding portion and the tip of the rod-shaped body, and holds the rod-shaped body relative to the holding portion until the tip of the rod-shaped body is inserted into the holding portion. A moving mechanism unit for moving is provided.

According to the above configuration, the rod-shaped body pierces the cell group held in the holding portion, so that the cells are transferred from the holding portion to the rod-shaped body. At this time, since the movement of the cell group is suppressed by the holding portion, the rod-shaped body easily sticks into the cell group. Therefore, it is possible to accurately hold the cell group in the rod-shaped body.

In the above configuration, the moving mechanism portion moves from a position where the holding portion holds the cell group arranged on the tray to a position where the tip portion of the holding portion and the tip portion of the rod-shaped body face each other. The position of the holding portion may be changed.

According to the above configuration, the cell group is held in the holding portion and carried from the tray to the rod-shaped body. Therefore, it is possible to smoothly accommodate the cell group in the needle-shaped portion.
In the above configuration, when the tip of the rod is inserted into the holding portion, the tip of the rod may be located inside the needle.

According to the above configuration, it is possible to shorten the time for the cell group to be exposed to the outside air when the cell group is accommodated in the needle-shaped portion, as compared with the case where the transplant is delivered outside the needle-shaped portion. Therefore, it is possible to protect the cell population.

In the above configuration, when the tip of the rod is inserted into the holding portion, the tip of the rod may protrude from the opening of the needle.
According to the above configuration, the cell group can be transferred from the holding portion to the rod-shaped body regardless of the outer diameter of the holding portion. Therefore, since the degree of freedom regarding the thickness of the holding portion is increased, the thickness of the holding portion can be set to a thickness more suitable for holding the cell group or a thickness that is easy to form.

The method for accommodating a transplant that solves the above-mentioned problems is a method for accommodating a transplant containing a cell group to be transplanted into a living body in a cell transplant device, and the cell transplant device is a needle extending in a tubular shape. The rod-shaped portion includes the needle-shaped portion having an opening at the tip end portion of the needle-shaped portion and a rod-shaped body extending along the extending direction of the needle-shaped portion inside the needle-shaped portion. The body is formed in the needle-shaped portion between the position where the tip of the rod-shaped body is arranged inside the needle-shaped portion and the position where the tip of the rod-shaped body protrudes from the opening of the needle-shaped portion. On the other hand, it is configured to be relatively movable, and the tip of the rod-shaped body pierces the cell group, and the cell group is inserted into the needle-shaped portion from the opening of the needle-shaped portion. ,including.

According to the above method, the implant is housed in the needle-shaped portion while being pierced by the rod-shaped body. Therefore, inside the needle-shaped portion, the orientation of the implant with respect to the needle-shaped portion is fixed. As a result, the transplant can be placed in a predetermined orientation with respect to the tissue in the living body, so that the placement of the transplant in the tissue of the transplant destination can be controlled.

In the above method, the cell group is the first cell group, the transplant contains the first cell group and the second cell group, and the tip of the rod-shaped body pierces the first cell group. Later, it may include piercing the second cell group and inserting the second cell group into the needle-shaped portion through the opening of the needle-shaped portion.

According to the above method, the transplant containing these cell groups is housed in the needle-shaped portion in a state where the rod-shaped body is stuck in the two cell groups. Therefore, inside the needle-shaped portion, the orientation of the transplant to the needle-shaped portion and the positional relationship between the cell groups are fixed. As a result, the arrangement of the transplanted product in the tissue of the transplanted destination can be controlled including the positional relationship between the cell groups.

In the above method, the tip of the rod-shaped body may pierce the cell group held by the tip of the holding portion extending in a cylindrical shape.
According to the above method, since the movement of the cell group is suppressed by the holding portion, the rod-shaped body easily sticks into the cell group. Therefore, the inclusion of the cell group in the needle-shaped portion proceeds smoothly.

The method for arranging the transplant to solve the above problem is a method of arranging the transplant containing the cell group from the cell transplant device into the living body, and the cell transplant device is a needle-shaped portion extending in a tubular shape. The rod-shaped body includes the needle-shaped portion having an opening at the tip end portion of the needle-shaped portion and a rod-shaped body extending along the extending direction of the needle-shaped portion inside the needle-shaped portion. Relative to the needle-shaped portion between the position where the tip of the rod-shaped body is arranged inside the needle-shaped portion and the position where the tip portion of the rod-shaped body protrudes from the opening of the needle-shaped portion. The needle-shaped part containing the implant pierced by the rod-shaped body is pierced into the living body, and the needle-shaped part is left in the living body and the needle-shaped part is left in the living body. Including pulling out.

According to the above method, the implant contained in the needle-shaped portion in a state of being pierced by the rod-shaped body enters the living body together with the needle-shaped portion and is left in the living body. Therefore, the orientation of the transplant in the needle-like part and the positional relationship between the cell groups are reflected in the arrangement of the transplant in the tissue of the transplant destination. Therefore, it is possible to control the placement of the transplant in the tissue of the transplant destination.

In the above method, after the needle-shaped portion is pulled out from the living body until the implant pierced by the rod-shaped body comes out from the opening of the needle-shaped portion, the rod-shaped body is pulled out from the implant. May include pulling out from.

According to the above method, with the passage of time, the tissue in the living body fills the circumference of the transplant. As a result, when the rod is pulled out, the implant is held down by the surrounding tissue, thus preventing the implant from moving with the rod.

In the above method, after the needle-shaped portion is pierced into a living body, the portion of the rod-shaped body in which the transplant is pierced may be separated from the other portion of the rod-shaped body.
According to the above method, the placement of the transplant in the living body can be completed without removing the rod-shaped body from the transplant. Therefore, the movement of the transplant is suppressed when the rod-shaped body is pulled out. In addition, a part of the rod-shaped body can be made to function as a member for inducing tissue formation from the implant.

According to the present invention, it is possible to control the arrangement of cell groups in the tissue to be transplanted.

The figure which shows the whole structure of the cell transplantation apparatus of 1st Embodiment. The figure which shows the cross-sectional structure of the needle-like part and the rod-like body provided with the cell transplantation apparatus of 1st Embodiment. The figure which shows the whole structure of the cell accommodating unit of 1st Embodiment. The figure which shows the cross-sectional structure of the holding part provided with the cell containment assisting apparatus of 1st Embodiment. The figure which shows the retention process of a cell group in the method of accommodating a transplant of 1st Embodiment. The figure which shows the cell group accommodating process in the method of accommodating a transplant of 1st Embodiment. The figure which shows the cell group accommodating process in the method of accommodating a transplant of 1st Embodiment. The figure which shows the cell group accommodating process in the method of accommodating a transplant of 1st Embodiment. The figure which shows the other example of the cell group accommodating step in the method of accommodating a transplant of 1st Embodiment. The figure which shows the other example of the cell group accommodating step in the method of accommodating a transplant of 1st Embodiment. The figure which shows the other example of the cell group accommodating step in the method of accommodating a transplant of 1st Embodiment. The figure which shows the holding process of the 2nd cell group in the method of accommodating a transplant of 1st Embodiment. The figure which shows the containment process of the 2nd cell group in the method of accommodating a transplant of 1st Embodiment. The figure which shows the containment process of the 2nd cell group in the method of accommodating a transplant of 1st Embodiment. The figure which shows the arrangement method of the transplant of 1st Embodiment. The figure which shows the arrangement method of the transplant of 1st Embodiment. The figure which shows the arrangement method of the transplant of 1st Embodiment. It is a modification of the cell transplantation apparatus of 1st Embodiment, and is the figure which shows the cross-sectional structure around the needle-like part in the cell transplantation apparatus provided with the stopper part. The figure which shows the state which the transplant is housed in the cell transplant device of the modification of 1st Embodiment. The figure which shows the state which the transplant is housed in the modification of the cell transplant device provided with the stopper part in 1st Embodiment. It is a modification of the cell transplantation apparatus of 1st Embodiment, and is the figure which shows the cross-sectional structure around the needle-like part in the cell transplantation apparatus provided with a plurality of needle-like portions. The figure which shows the whole structure of the cell transplantation apparatus of 2nd Embodiment. The figure which shows the arrangement method of the transplant of 2nd Embodiment.

(First Embodiment)
With reference to FIGS. 1 to 21, a first embodiment of a cell transplant device, a cell accommodating unit, a method of accommodating a transplant, and a method of arranging a transplant will be described. The cell transplantation apparatus of this embodiment is used for transplanting a transplant containing a cell group into a living body. The target area for transplantation is at least one of intracutaneous and subcutaneous, or in a tissue such as an organ. In the present embodiment, the "living body" includes not only the body or tissue of an organism but also an artificial biological model that imitates the body or tissue. That is, the cell transplantation apparatus of the present embodiment can not only transplant a transplant into an organism, but also transplant the transplant into a biological model.

[Transplant]
The transplant comprises one or more cell populations. A cell group is a collection of multiple cells. The cell group may be an aggregate of a plurality of aggregated cells, or may be an aggregate of a plurality of cells bound by cell-cell binding. These aggregates may be covered with a gel-like support. Further, a cell group may be formed by dispersing a plurality of cells on a gel-like support. The support consists of an extracellular matrix such as collagen, for example.

The cell included in the cell group may be an undifferentiated cell, a cell in which differentiation has been completed, or the cell group may include an undifferentiated cell and a differentiated cell. The cell group is, for example, a cell mass (spheroid), a primordium, a tissue, an organ, an organoid, a mini-sized organ, or the like. The transplant may contain a plurality of cell groups composed of different types of cells.

The implant has the ability to act on the tissue formation of the organism by being placed in the area of interest for transplantation in the organism. An example of a cell group contained in a transplant having such ability is a cell aggregate containing cells having stem cell properties.

The implant contributes to hair growth or growth, for example by being placed intradermally or subcutaneously. Such implants have the ability to function as hair follicle organs, differentiate into hair follicle organs, induce or promote the formation of hair follicle organs, or induce or promote hair formation in hair follicles. .. Furthermore, the cell group included in the transplant may include cells that contribute to the control of coat color, such as pigment cells or stem cells that differentiate into pigment cells. In addition, the cell group may include vasculature cells.

In one example of this embodiment, the implant comprises a hair follicle primordium, which is a primitive hair follicle organ. The hair follicle primordium contains a cell group consisting of mesenchymal cells and a cell group consisting of epithelial line cells, and these two cell groups are in contact with each other. In the hair follicle organ, hair follicle head cells, which are mesenchymal cells, induce the differentiation of hair follicle epithelial stem cells, and hair matrix cells repeat division in the hair bulb formed thereby to form hair. To. Hair follicle primordium differentiates into these hair follicle organs.

The hair follicle primordia contained in the implant includes, for example, mesenchymal cells derived from mesenchymal tissues such as the hair papilla and epithelial cells derived from epithelial tissues located in the bulge region and the base of the hair bulb, respectively. Two types of cell groups are formed by culturing, and they are formed by contacting these cell groups. However, the method for producing a hair follicle primordium is not limited to the above example. Further, the origin of the mesenchymal cells and epithelial cells used for producing the hair follicle primordia is not limited, and these cells may be cells derived from the hair follicle organ, and the hair follicle organ is a cell. It may be a cell derived from a different organ or a cell derived from a pluripotent stem cell.

In addition, the transplant containing the hair follicle primordium contains a cell group of mesenchymal cells and a cell group of epithelial cells, as well as a cell group that contributes to the engraftment and improvement of the function of the hair follicle primordium. May be good. Such a cell group is, for example, a cell group related to hair color, a cell group containing vascular cells, a cell group releasing a growth factor, and the like.
In addition, the transplanted product may contain a member that assists the transplantation and engraftment of the cell group together with the cell group. Such members are, for example, gel beads that slowly release growth factors.

[Cell transplant device]
The overall configuration of the cell transplantation apparatus will be described with reference to FIG. As shown in FIG. 1, the cell transplantation device 100 includes a needle-shaped portion 10 extending in a cylindrical shape and a support portion 20 for supporting the needle-shaped portion 10. Further, the cell transplantation device 100 includes a rod-shaped body 30 located inside the needle-shaped portion 10.

The needle-shaped portion 10 extends along one direction and has an opening 11 at its tip. The outer shape of the needle-shaped portion 10 is not particularly limited as long as the tip portion of the needle-shaped portion 10 has a shape capable of piercing a target site for transplantation such as skin in a living body. The needle-shaped portion 10 has, for example, a shape in which the tip portion of the cylinder is cut diagonally with respect to the extending direction thereof, and the tip portion of the needle-shaped portion 10 is sharp.

The support portion 20 may be formed integrally with the needle-shaped portion 10, or may be a member formed separately from the needle-shaped portion 10. The outer shape of the support portion 20 is not particularly limited. When the support portion 20 is integrally formed with the needle-shaped portion 10, the needle-shaped portion 10 protrudes from the support portion 20.

When the support portion 20 is a member formed separately from the needle-shaped portion 10, for example, the needle-shaped portion 10 is assembled to the support portion 20 by passing the needle-shaped portion 10 through the hole of the support portion 20. Has been done. The tip of the needle-shaped portion 10 and its vicinity protrude from the support portion 20 along the extending direction of the needle-shaped portion 10.

Regardless of whether the needle-shaped portion 10 and the support portion 20 are integrally formed or are separate members, at least the portion of the needle-shaped portion 10 protruding from the support portion 20 is transplanted in a living body. The part that enters the target area is included. The material of the needle-shaped portion 10 and the support portion 20 is not particularly limited, and the needle-shaped portion 10 and the support portion 20 are formed of, for example, a metal or a resin.

The rod-shaped body 30 extends along the extending direction of the needle-shaped portion 10. The rod-shaped body 30 is configured to be movable relative to the needle-shaped portion 10 along the extending direction of the needle-shaped portion 10. The rod-shaped body 30 may have a linear shape extending in the extending direction of the needle-shaped portion 10, or may have a curved shape such as an arc shape or a wavy line extending in the extending direction of the needle-shaped portion 10. The cross-sectional shape of the rod-shaped body 30 may be a circular shape, an elliptical shape, a polygonal shape, or an indefinite shape other than the geometric shape having convex portions and concave portions. The rod-shaped body 30 has a tip having a shape capable of piercing the implant. The tip portion of the rod-shaped body 30 may be a plane orthogonal to the extending direction of the needle-shaped portion 10, a plane intersecting the extending direction of the needle-shaped portion 10, or a curved surface protruding in the extending direction of the needle-shaped portion 10. However, it may be a curved surface that is recessed in the direction opposite to the extending direction of the needle-shaped portion 10. The implant is housed inside the needle-shaped portion 10 with the rod 30 piercing the implant. The state in which the rod-shaped body 30 pierces the implant may be a state in which the rod-shaped body 30 penetrates a single transplant, a state in which the rod-shaped body 30 penetrates a plurality of implants, or a rod-shaped body. The tip of the body 30 may be located inside one implant. The form in which the rod 30 penetrates the implant is preferable from the viewpoint of stabilizing the holding of the implant by the rod 30. The form in which the tip of the rod-shaped body 30 is located inside one implant is preferable from the viewpoint of suppressing the load on the implant.

When the tip of the rod-shaped body 30 is located inside one implant, the length of the portion of the rod-shaped body 30 located inside the implant in the extending direction of the needle-shaped portion 10 is the rod-shaped body 30. It may be long enough to hold one implant, for example, 10 μm or more and 300 μm or less. When the tip of the rod-shaped body 30 is located inside one implant, the length of the portion of the rod-shaped body 30 located inside the implant in the extending direction of the needle-shaped portion 10 is the length of the implant. It may be 80% or more, preferably 50% or more of the length of the implant.

The cell transplantation device 100 further includes a position changing portion 40 that changes the position of the rod-shaped body 30 with respect to the needle-shaped portion 10.
The position changing portion 40 includes a structure for moving the rod-shaped body 30 relative to the needle-shaped portion 10. The operation of the position changing unit 40 may be performed manually, or the position changing unit 40 may include an electronic component such as a motor, and the operation of the position changing unit 40 may be performed by electrical control.

With reference to FIG. 2, a detailed configuration relating to the dimensions of the rod-shaped body 30 will be described with reference to an example of the rod-shaped body 30. As shown in FIG. 2, an example of the rod-shaped body 30 is a skewer-shaped structure having a linear shape extending along the extending direction of the needle-shaped portion 10. The material of the rod-shaped body 30 is not particularly limited, and the rod-shaped body 30 is made of, for example, a metal or a resin.

The rod-shaped body 30 is a position where the tip portion of the rod-shaped body 30 is arranged inside the needle-shaped portion 10 and a position where the tip portion of the rod-shaped body 30 protrudes from the opening 11 of the needle-shaped portion 10 to the outside of the needle-shaped portion 10. It is relatively movable with respect to the needle-shaped portion 10. The movement of the rod-shaped body 30 with respect to the needle-shaped portion 10 is performed based on the operation of the position changing portion 40 described above.

It is preferable that the tip of the rod-shaped body 30 is sharp. In other words, it is preferable that the rod-shaped body 30 becomes thinner toward the tip and the tip of the rod-shaped body 30 is point-shaped. According to such a configuration, the rod-shaped body 30 is easily pierced by the cell group Cg containing the transplant.

On the other hand, if the tip of the rod 30 is thin enough to pierce the cell group Cg, the thickness of the rod 30 may be constant, and the tip of the rod 30 is flat. May be good. For example, the tip of the rod 30 may be formed to have a rigidity such that the tip of the rod 30 does not deform when the rod 30 pierces the cell group Cg.

The outer diameter do2 of the rod-shaped body 30 is the maximum length that a straight line located in the cross section of the rod-shaped body 30 can take. The cross section of the rod-shaped body 30 is a plane orthogonal to the extending direction of the rod-shaped body 30. The outer diameter do2 of the rod-shaped body 30 is the maximum length at the portion of the rod-shaped body 30 that is pierced by the cell group Cg when the rod-shaped body 30 penetrates the cell group Cg. When the tip of the rod-shaped body 30 is located inside the cell group Cg, the outer diameter do2 of the rod-shaped body 30 is the maximum length in the portion of the rod-shaped body 30 located inside the cell group Cg, and the cell. In the portion not located inside the group Cg, the straight line located in the cross section of the rod-shaped body 30 may be longer than the outer diameter do2.

For example, when the rod-shaped body 30 is columnar and the rod-shaped body 30 penetrates the cell group Cg, the outer diameter do2 of the rod-shaped body 30 is the maximum in the portion of the rod-shaped body 30 to be pierced by the cell group Cg. The diameter. When the rod-shaped body 30 is columnar and the tip of the rod-shaped body 30 is located inside the cell group Cg, the outer diameter do2 of the rod-shaped body 30 is located inside the cell group Cg in the rod-shaped body 30. The maximum length in the part.

For example, when the rod-shaped body 30 has an elliptical columnar shape and the rod-shaped body 30 penetrates the cell group Cg, the outer diameter do2 of the rod-shaped body 30 is the major axis in the portion of the rod-shaped body 30 to be pierced by the cell group Cg. Is the maximum value of. When the rod-shaped body 30 has an elliptical columnar shape and the tip of the rod-shaped body 30 is located inside the cell group Cg, the outer diameter do2 of the rod-shaped body 30 is located inside the cell group Cg in the rod-shaped body 30. It is the maximum value of the major axis in the part.

For example, when the rod-shaped body 30 has a square columnar shape and the rod-shaped body 30 penetrates the cell group Cg, the outer diameter do2 of the rod-shaped body 30 is a cross section of a portion of the rod-shaped body 30 that is pierced by the cell group Cg. The maximum length of the diagonal within. When the rod-shaped body 30 has a square columnar shape and the tip of the rod-shaped body 30 is located inside the cell group Cg, the outer diameter do2 of the rod-shaped body 30 is located inside the cell group Cg in the rod-shaped body 30. The maximum length of the diagonal in the cross section of the portion.

Whether the rod 30 penetrates the cell group Cg, the tip of the rod 30 is located inside the cell group Cg, or the tip of the rod 30 is sharp, it is sharp. Even if the rod-shaped body 30 is not provided, the tip portion of the rod-shaped body 30 may have a size capable of piercing the cell group Cg by the rod-shaped body 30. In other words, the cell group Cg may have a size capable of piercing the rod-shaped body 30 into the cell group Cg. Whether the rod-shaped body 30 penetrates the cell group Cg or the tip of the rod-shaped body 30 is located inside the cell group Cg, the outer diameter do2 of the rod-shaped body 30 forms an aggregate of cells in the cell group Cg. It is preferable that the cell group Cg has a size that does not easily come off from the rod-shaped body 30.

Hereinafter, the relationship between the size of the cell group Cg suitable for piercing the rod-shaped body 30 into the cell group Cg and the thickness of the rod-shaped body 30 will be described.
For a suitable puncture of the rod 30 into the cell group Cg, the outer diameter do2 is in the direction corresponding to the radial direction of the rod 30, regardless of whether the tip of the rod 30 is sharp or not. It may be smaller than the width of the cell group Cg. Specifically, when the direction in which the rod-shaped body 30 enters the cell group Cg is the piercing direction, the outer shape of the cell group Cg in the state where the rod-shaped body 30 is not pierced is projected onto a plane orthogonal to the piercing direction. It suffices if the projected image in the above can include a circle having the same diameter as the outer diameter do2. This is applicable regardless of whether the cell group Cg has a shape that can be approximated to a solid such as a sphere or an ellipsoid, or the shape of the cell group Cg is irregular.

Further, the outer diameter do2 of the rod-shaped body 30 is preferably 0.5 times or less the width of the cell group Cg. With such a configuration, the rod-shaped body 30 is likely to be pierced by the cell group Cg not only when the tip portion of the rod-shaped body 30 is sharp but also when the tip portion of the rod-shaped body 30 is not sharpened. Further, when the rod-shaped body 30 pierces the cell group Cg, it is possible to suppress the load on the cell group Cg. Further, when the rod-shaped body 30 penetrates the cell group Cg, it is difficult to disassemble the cells in the cell group Cg by the penetration of the rod-shaped body 30. Specifically, when the outer shape of the cell group Cg in which the rod-shaped body 30 is not pierced is projected onto a plane orthogonal to the piercing direction, the projected image contains a circle having a diameter more than twice the outer diameter do2. It is preferable to do so.

When the cell group Cg has a shape that can be approximated to a solid such as a sphere or an ellipsoid, the width of the cell group Cg is the outer shape of the cell group Cg in a state where the rod-shaped body 30 is not pierced in the piercing direction. It can be regarded as the diameter of the inscribed circle of the projected image when projected on a plane orthogonal to. For example, when the cell group Cg has a substantially spherical shape extending isotropically from the center, the width of the cell group Cg corresponds to the diameter of the largest sphere inscribed in the cell group Cg. Further, when the cell group Cg has a substantially oblong ellipsoid shape and its major axis direction is the puncture direction, the diameter of the inscribed circle of the cell group Cg when viewed along the major axis direction, for example, an oblong ellipsoid. The length corresponding to twice the short radius in is corresponding to the width of the cell group Cg.

The outer diameter do2 of the rod-shaped body 30 is preferably 0.4 times or less the inner diameter di1 of the needle-shaped portion 10. As a result, when the tip of the rod-shaped body 30 is located inside the needle-shaped portion 10, there is a sufficient gap between the rod-shaped body 30 and the inner surface of the needle-shaped portion 10 for accommodating the cell group Cg. Secured. Therefore, the cell group Cg is smoothly contained, and the load on the cell group Cg is suppressed when the cell group Cg is housed in the needle-shaped portion 10. When the inner diameter of the needle-shaped portion 10 is not constant, the inner diameter di1 is the minimum value of the inner diameter of the portion of the needle-shaped portion 10 protruding from the support portion 20.

Since the cell group Cg has flexibility, even when the cell group Cg is wider than the inner diameter di1 of the needle-shaped portion 10 in a state where the rod-shaped body 30 pierces the cell group Cg, the needle-shaped portion is formed. It is possible to contain the cell group Cg inside 10. For smooth accommodation of the cell group Cg, the inner diameter di1 of the needle-shaped portion 10 is preferably 0.4 times or more the diameter of the cell group Cg.

The diameter of the cell group Cg is the circumscribed circle of the projected image when the outer shape of the cell group Cg in a state where the rod-shaped body 30 is not pierced is projected onto a plane orthogonal to the direction in which the cell group Cg is housed in the needle-shaped portion 10. The diameter of the circle. The direction in which the cell group Cg is housed in the needle-shaped portion 10 is a direction along the extending direction of the needle-shaped portion 10 and the rod-shaped body 30, and is a direction along the straight line extending in the piercing direction.

When the cell group Cg is a cell mass and the transplant contributes to hair growth or hair growth, the diameter of the cell group Cg is about 0.1 mm or more and 1 mm or less. In this case, the outer diameter do2 of the rod-shaped body 30 is selected from the range of, for example, 10 μm or more and 250 μm or less, and the inner diameter di1 of the needle-shaped portion 10 is selected from the range of, for example, 0.2 mm or more and 1.5 mm or less.

In a state where the tip portion of the rod-shaped body 30 is located inside the needle-shaped portion 10, the length of the portion of the rod-shaped body 30 located inside the portion of the needle-shaped body 10 protruding from the support portion 20 is determined. It is set according to the depth at which the cell group Cg is placed in the living body. For example, when the transplanted product contributes to hair growth or hair growth and the target area for transplantation is the dermis layer of the skin, the length is selected from the range of 1 mm or more and 10 mm or less.

In one example, when the needle-shaped portion 10 is pierced into the skin along a direction orthogonal to the surface of the skin and the cell group Cg is arranged in the dermis layer, the length of the rod-shaped body 30 is set to 3 mm. In another example, when the needle-shaped portion 10 is pierced into the skin along a direction inclined with respect to the surface of the skin and the cell group Cg is arranged in the dermis layer, the length of the rod-shaped body 30 is 9 mm.

[Cell containment unit]
The overall configuration of the cell containment unit will be described with reference to FIG. As shown in FIG. 3, the cell containment unit 120 includes the above-mentioned cell transplantation device 100 and the cell containment assisting device 110. The cell storage assisting device 110 assists in accommodating a group of cells arranged in a tray such as a culture vessel in the needle-shaped portion 10 of the cell transplanting device 100.

The cell storage assisting device 110 includes a cylindrical holding portion 60 extending along one direction, a rearranging changing portion 70 that changes the position of the holding portion 60 with respect to the needle-shaped portion 10, and a suction unit that sucks the inside of the holding portion 60. It is equipped with 80.

Based on the fact that the inside of the holding portion 60 is sucked, the holding portion 60 attracts the cell group to the tip portion thereof and holds the cell group. The outer shape of the holding portion 60 is not particularly limited, and the holding portion 60 may be cylindrical. For example, the holding portion 60 has a cylindrical shape, and the tip surface of the holding portion 60 is a plane orthogonal to the extending direction of the holding portion 60.

The arrangement changing portion 70 changes the position of the holding portion 60 with respect to the needle-shaped portion 10, for example, by moving the holding portion 60. In this case, the arrangement changing portion 70 includes a support member that movably supports the holding portion 60, and a mechanism for moving the holding portion 60 along the support member.

Specifically, the rearrangement changing unit 70 moves the position of the holding unit 60 from the holding position, which is the position for the holding unit 60 to hold the cell group arranged on the tray, to the tip portion of the holding unit 60 and the cells. The accommodation position is changed to the position where the tip of the rod-shaped body 30 in the transplanting device 100 faces. For example, the rearrangement changing unit 70 moves the holding unit 60 from the holding position to the accommodating position by moving the holding unit 60 in a direction along the extending direction of the holding unit 60 and a direction orthogonal to this direction.

When changing the position of the holding unit 60 from the holding position to the accommodation position, only the holding unit 60 may move among the holding unit 60 and the cell transplanting device 100, or the holding unit 60 and the cell transplanting device 100 Both may move, or only the cell transplantation device 100 may move. That is, the cell accommodating assisting device 110 includes an installation portion (not shown), which is a portion where the cell transplantation device 100 is installed, but the installation portion may be movable. When the installation unit moves, the arrangement change unit 70 includes a mechanism for moving the installation unit. The operation of the arrangement changing unit 70 may be performed manually, or the arrangement changing unit 70 may include an electronic component such as a motor and the operation of the arrangement changing unit 70 may be performed by electrical control.

The suction unit 80 includes a mechanism such as a pump that sucks air. Further, the suction unit 80 includes a liquid storage unit that stores the liquid material sucked when the cell group is held by the holding unit 60. By the operation of the suction unit 80, it may be possible to pressurize the inside of the holding unit 60 using air pressure in addition to the suction inside the holding unit 60. When pressurizing, the suction unit 80 may include a mechanism such as a compressor.

The detailed configuration of the holding unit 60 will be described with reference to FIG. As shown in FIG. 4, the holding portion 60 holds the cell group Cg at the tip of the holding portion 60. Specifically, by sucking the inside of the holding portion 60, the cell group Cg is attracted to the tip portion of the holding portion 60, and the cell group Cg is held by the holding portion 60 so as to be in contact with the holding portion 60. The material of the holding portion 60 is not particularly limited, and the holding portion 60 is made of, for example, a metal or a resin.

The inner diameter di4 of the holding portion 60 is so small that the entire cell group Cg does not enter the inside of the holding portion 60. On the other hand, it is preferable that the inner diameter di4 of the holding portion 60 is large enough to exert a sufficient suction force to attract the cell group Cg. The inner diameter di4 of the holding portion 60 is larger than the outer diameter do2 of the rod-shaped body 30, and the rod-shaped body 30 can be inserted into the inside of the holding portion 60 from the opening of the tip portion of the holding portion 60. When the inner diameter of the holding portion 60 is not constant, the inner diameter di4 is the minimum value of the inner diameter of the holding portion 60, that is, the inner diameter of the narrowest portion in the holding portion 60.

The outer diameter do4 of the holding portion 60 may be smaller than the inner diameter di1 of the needle-shaped portion 10, and the holding portion 60 may be inserted into the inside of the needle-shaped portion 10. Alternatively, the outer diameter do4 of the holding portion 60 may be equal to or larger than the inner diameter di1 of the needle-shaped portion 10, and the holding portion 60 may not be inserted into the inside of the needle-shaped portion 10. When the outer diameter of the holding portion 60 is not constant, the outer diameter do4 is the outer diameter at the tip of the holding portion 60.

As described above, when the cell group Cg is a cell mass and the transplant contributes to hair growth or hair growth, the diameter of the cell group Cg is about 0.1 mm or more and 1 mm or less. In this case, the inner diameter di4 of the holding portion 60 is selected from, for example, a range of 0.05 mm or more and 1.1 mm or less.

[Transplant storage method]
With reference to FIGS. 5 to 14, a method of accommodating a transplant into the cell transplant device 100 using the cell accommodating unit 120 will be described. The method for accommodating the transplant is a holding step in which the holding unit 60 of the cell accommodating assisting device 110 holds the cell group Cg, and the cell group Cg is transferred from the holding unit 60 to the rod-shaped body 30 of the cell transplanting device 100, and a needle is used. The inclusion step, which is a step of accommodating the cell group Cg inside the shape portion 10, is included.

First, the holding process will be described with reference to FIG. The cell group Cg is arranged in a tray 130 such as a culture container together with a protective solution which is a liquid material that protects the cell group Cg. For example, the cell group Cg is placed in the recess 131 of the tray 130 together with the protective liquid. The arrangement of the cell group Cg and the protective solution in the tray 130 is not limited to the form in which the cell group Cg and the protective solution are placed in the recess 131. For example, the cell group Cg and the protective solution may be arranged on the plane of the tray 130.

The protective solution may have a composition that does not easily inhibit the survival of cells, and is preferably composed of a substance having a small effect on the living body when injected into the living body. For example, the protective liquid is a liquid that protects the skin such as physiological saline, petrolatum or cosmetic water, or a mixture of these liquids. The protective liquid may contain additive components such as nutritional components. Further, when the tray 130 is a culture vessel and the cell group Cg is cultured in the tray 130, the protective liquid may be a medium for culturing cells or a liquid exchanged from the medium. You may. The protective liquid can be a sol-like body, a gel-like body, a low-viscosity fluid, or a high-viscosity fluid.

In the holding step, the tip portion of the holding portion 60 is brought closer to the cell group Cg arranged in the tray 130 by the operation of the rearrangement changing portion 70 in the cell accommodating assisting device 110. As a result, the holding portion 60 is arranged at the holding position. The position where the tip of the holding portion 60 faces the cell group Cg in the tray 130 is the holding position. For example, the opening surface of the recess 131 of the tray 130 and the tip of the holding portion 60 face each other, and the tip of the holding portion 60 is inserted into the recess 131, so that the holding portion 60 is arranged at the holding position. Then, the inside of the holding portion 60 is sucked by the operation of the suction portion 80. As a result, the cell group Cg is attracted to the tip of the holding portion 60, and the cell group Cg is held by the holding portion 60.

Next, the accommodating process will be described. In the accommodating step, the cell group Cg is transferred from the holding portion 60 to the rod-shaped body 30 inside the needle-shaped portion 10 or outside the needle-shaped portion 10. First, a mode in which the cell group Cg is delivered inside the needle-shaped portion 10 will be described. In this case, the outer diameter do4 of the holding portion 60 is smaller than the inner diameter di1 of the needle-shaped portion 10, and the holding portion 60 can be inserted into the inside of the needle-shaped portion 10.

In the accommodating step, first, the holding portion 60 is arranged at the accommodating position as shown in FIG. 6 by the operation of the arrangement changing portion 70. The accommodating position is a position where the holding portion 60 is aligned with the extending directions of the needle-shaped portion 10 and the rod-shaped body 30, and the tip portion of the holding portion 60 faces the opening 11 of the needle-shaped portion 10 and the tip portion of the rod-shaped body 30. .. In the state where the holding portion 60 is arranged at the accommodation position, the tip portion of the rod-shaped body 30 is located inside the needle-shaped portion 10.

In the drawings, for ease of understanding, each part is shown so that the opening 11 of the needle-shaped part 10 is directed downward and the holding part 60 is located under the needle-shaped part 10, but the holding part is held. The relationship between the orientation of the portion 60 and the needle-shaped portion 10 and the vertical direction is not particularly limited. The holding portion 60 may be located on the needle-shaped portion 10 with the opening 11 of the needle-shaped portion 10 facing upward, and the extending direction of the holding portion 60 and the needle-shaped portion 10 is different from the vertical direction. You may.

Subsequently, as shown in FIG. 7, the tip portion of the holding portion 60 holding the cell group Cg is inserted into the needle-shaped portion 10. Along with this, the tip of the rod-shaped body 30 pierces the cell group Cg. The tip of the rod-shaped body 30 penetrating the cell group Cg is inserted inside the holding portion 60.

Then, when the suction in the holding portion 60 is stopped, the holding of the cell group Cg by the holding portion 60 is released, and as shown in FIG. 8, the tip portion of the holding portion 60 is pulled out from the needle-shaped portion 10. .. At this time, the release of the retention of the cell group Cg may be assisted by pressurizing the inside of the holding portion 60.
As a result, the cell group Cg is housed inside the needle-shaped portion 10 in a state where the rod-shaped body 30 is pierced by the cell group Cg.

The inside of the needle-shaped portion 10 is filled with a liquid substance that protects the cell group Cg, and in a state where the cell group Cg is contained in the needle-shaped portion 10, the liquid substance is formed around the cell group Cg. May exist. The liquid material has a structure similar to the structure exemplified as the above-mentioned protective liquid. Further, when the holding portion 60 enters and exits the needle-shaped portion 10, the holding portion 60 may move, the needle-shaped portion 10 and the rod-shaped body 30 may move, or both of them may move. .. The movement of the holding portion 60, the needle-shaped portion 10, and the rod-shaped body 30 is performed based on the operation of the rearrangement changing portion 70.

Next, a mode in which the cell group Cg is delivered outside the needle-shaped portion 10 will be described. In this case, the outer diameter do4 of the holding portion 60 may be smaller than the inner diameter di1 of the needle-shaped portion 10, or may be larger than the inner diameter di1 of the needle-shaped portion 10.

First, the holding portion 60 is arranged at the accommodation position in the same manner as in the case where the cell group Cg is delivered inside the needle-shaped portion 10. Then, the rod-shaped body 30 is moved by the operation of the position changing portion 40 of the cell transplanting device 100, and as shown in FIG. 9, the tip portion of the rod-shaped body 30 is moved from the opening 11 of the needle-shaped portion 10 to the outside of the needle-shaped portion 10. Come out to. The tip of the rod-shaped body 30 protruding from the needle-shaped portion 10 pierces the cell group Cg held by the holding portion 60. The tip of the rod-shaped body 30 penetrating the cell group Cg is inserted inside the holding portion 60.

Then, when the suction in the holding portion 60 is stopped, the holding of the cell group Cg by the holding portion 60 is released, and as shown in FIG. 10, the tip portion of the rod-shaped body 30 is inside the needle-shaped portion 10. Be drawn in. Along with this, the cell group Cg is also drawn into the needle-shaped portion 10, and the cell group Cg is housed inside the needle-shaped portion 10 with the rod-shaped body 30 stuck in the cell group Cg. Pressurization in the holding portion 60 may assist in releasing the holding of the cell group Cg.

The inside of the needle-shaped portion 10 is filled with a liquid substance that protects the cell group Cg, and in a state where the cell group Cg is contained in the needle-shaped portion 10, the liquid substance is formed around the cell group Cg. May exist. Further, instead of moving the rod-shaped body 30 after the holding portion 60 is arranged at the accommodation position, the holding portion is made into a state in which the tip portion of the rod-shaped body 30 protrudes from the opening 11 of the needle-shaped portion 10. With the 60 placed in the containment position, the rod 30 may pierce the cell group Cg.

Further, when the cell group Cg is delivered outside the needle-shaped portion 10, the holding step and the accommodating step may be performed with the cell group Cg arranged on the tray 130. Specifically, as shown in FIG. 11, the tip of the holding portion 60 is arranged so as to face the cell group Cg through an openable / closable hole provided at the bottom of the recess 131 in the tray 130. The hole is closed before the holding step and is opened in the holding step. Then, by sucking the inside of the holding portion 60, the cell group Cg is held at the tip portion of the holding portion 60. After that, the cell transplantation device 100 is arranged so that the tip of the holding portion 60 faces the opening 11 of the needle-shaped portion 10 and the tip of the rod-shaped body 30, and the tip of the rod-shaped body 30 protruding from the opening 11 of the needle-shaped portion 10 is arranged. The part pierces the cell group Cg. That is, the rod-shaped body 30 enters the recess 131 through the opening of the recess 131 and pierces the cell group Cg held in the holding portion 60 at the bottom of the recess 131.

According to such a configuration, the load required for moving the holding portion 60 from the holding position to the accommodating position is reduced, and the cell group Cg is suppressed from being exposed to the outside air during such movement, so that the cell group Cg is protected. Is possible.

As described above, when the number of cell groups Cg contained in the transplant is one, one cell group Cg is contained in the needle-shaped portion 10, so that the transplant can be accommodated in the needle-shaped portion 10. Complete. On the other hand, when the transplant contains a plurality of cell group Cg, the retention step and the containment step are repeated for the number of cell group Cg.

For example, the case where the transplant Tg contains two cell groups Cg will be described subsequently. For the first cell group Cg1, which is the first cell group Cg, the holding step and the accommodating step are performed as described above, and after the first cell group Cg1 is accommodated in the needle-shaped portion 10, the second cell. For the second cell group Cg2, which is the group Cg, a retention step and a containment step are performed.

That is, as shown in FIG. 12, by arranging the holding portion 60 at the holding position, the holding portion 60 is brought closer to the second cell group Cg2 arranged in the tray 130. Then, by sucking the inside of the holding portion 60, the second cell group Cg2 is held by the holding portion 60.

Subsequently, as shown in FIG. 13, the holding portion 60 is arranged at the accommodation position, and the tip portion of the holding portion 60 holding the second cell group Cg2 is inserted into the needle-shaped portion 10 to form a rod shape. The tip of the body 30 pierces the second cell group Cg2. The rod-shaped body 30 already holds the first cell group Cg1 by being pierced through the first cell group Cg1, and the portion of the rod-shaped body 30 on the tip side of the rod-shaped body 30 with respect to the first cell group Cg1 , Stings into the second cell group Cg2.

Then, as shown in FIG. 14, by stopping the suction in the holding portion 60, the holding of the second cell group Cg2 by the holding portion 60 is released, and the tip portion of the holding portion 60 is the needle-shaped portion 10. Be pulled out of.

In addition, although FIG. 13 and FIG. 14 showed the form in which the delivery of the second cell group Cg2 is performed inside the needle-shaped portion 10, the delivery of the second cell group Cg2 is performed in the needle-shaped portion 10 as described above. It may be done externally. Further, the holding portion 60 holding the first cell group Cg1 and the holding portion 60 holding the second cell group Cg2 may be different holding portions 60.

As a result, the second cell group Cg2 is housed inside the needle-shaped portion 10. As a result, the transplant Tg containing the first cell group Cg1 and the second cell group Cg2 is housed inside the needle-shaped portion 10 in a state of being stuck in the rod-shaped body 30. The first cell group Cg1 and the second cell group Cg2 are arranged along the rod-shaped body 30, and the second cell group Cg2 is located on the side where the tip of the rod-shaped body 30 is located with respect to the first cell group Cg1.

When the rod-shaped body 30 pierces the second cell group Cg2, the rod-shaped body 30 and the holding portion are inserted so that the rod-shaped body 30 pierces the second cell group Cg2 until the position where the second cell group Cg2 comes into contact with the first cell group Cg1. By adjusting the position with 60, the first cell group Cg1 and the second cell group Cg2 can be brought into contact with each other in the transplanted Tg.

In the state where the rod-shaped body 30 is stuck in the first cell group Cg1 and the second cell group Cg2, the first cell group Cg1 and the second cell group Cg2 may not be in contact with each other. When the rod-shaped body 30 pierces the second cell group Cg2, the positions of the rod-shaped body 30 and the holding portion 60 are adjusted so that a predetermined distance is provided between the first cell group Cg1 and the second cell group Cg2. You may.

When the transplant Tg contains a hair follicle primordium, the first cell group Cg1 is a cell mass of epithelial cells and the second cell group Cg2 is a cell mass of mesenchymal cells. Then, in the transplant Tg housed in the needle-shaped portion 10, the first cell group Cg1 and the second cell group Cg2 come into contact with each other.

In the above configuration, the cell accommodating unit 120 faces the tip of the holding portion 60 and the tip of the rod-shaped body 30 until the tip of the rod-shaped body 30 is inserted into the holding portion 60. A moving mechanism unit for moving the rod-shaped body 30 relative to 60 is provided. When the movement of the holding portion 60 to the accommodation position and the movement of the rod-shaped body 30 with respect to the holding portion 60 when the rod-shaped body 30 pierces the cell group Cg are performed only by the rearrangement portion 70, that is, the needle is used for these movements. When the rod-shaped body 30 is not moved with respect to the shaped portion 10, the moving mechanism portion is composed of a rearrangement changing portion 70 of the cell accommodating assisting device 110. On the other hand, when the rod-shaped body 30 is moved with respect to the needle-shaped portion 10 during these movements, the movement mechanism portion is composed of a rearrangement changing portion 70 of the cell accommodating assisting device 110 and a position changing portion 40 of the cell transplanting device 100. ..

Further, the cell accommodating unit 120 includes a control unit that controls the holding position of the cell group Cg in the rod-shaped body 30, in other words, the position of the cell group Cg pierced by the rod-shaped body 30 along the rod-shaped body 30. You may. The control unit controls the position of the rod-shaped body 30 with respect to the holding portion 60 when the rod-shaped body 30 pierces the cell group Cg by controlling the operation of the movement mechanism unit, whereby the cell group Cg in the rod-shaped body 30 is controlled. Control the holding position.

For example, when the transplant Tg contains two cell groups Cg, the control unit sets the holding position of the first cell group Cg1 in the rod-shaped body 30 to the length of the portion of the rod-shaped body 30 that protrudes from the first cell group Cg1. Is controlled to be larger than the length along the puncture direction in the second cell group Cg2. Further, the control unit controls the holding position of the second cell group Cg2 in the rod-shaped body 30 to the position where the first cell group Cg1 and the second cell group Cg2 are in contact with each other along the rod-shaped body 30.

[How to place the transplant]
With reference to FIGS. 15 to 17, a method of arranging the transplanted material in a living body using the cell transplantation device 100 will be described. The method for accommodating the transplant and the method for arranging the transplant are included in the method for using the cell transplant device 100.

After the transplant Tg is housed in the needle-shaped portion 10 by the method for accommodating the transplant described above, the cell transplant device 100 is carried to the transplant site Sk, which is, for example, the skin of the head of a living body. Then, as shown in FIG. 15, the transplantation site Sk is stabbed by the needle-shaped portion 10. At this time, the tip of the rod-shaped body 30 and the transplant Tg are located inside the needle-shaped portion 10, and the tip of the needle-shaped portion 10 is located at the tip of the cell transplanting device 100. Since the tip of the needle-shaped portion 10 has a shape that easily sticks into the living body, the needle-shaped portion 10 can smoothly enter the transplantation site Sk. The needle-shaped portion 10 enters the transplantation site Sk until the vicinity of the tip portion of the needle-shaped portion 10 is arranged in the target area for transplantation.

Next, as shown in FIG. 16, the rod-shaped body 30 is moved relative to the needle-shaped portion 10, and the portion of the rod-shaped body 30 holding the transplant Tg is formed from the opening 11 of the needle-shaped portion 10. It is said to be out. Specifically, the positions of the rod 30 and the implant Tg remain unchanged, and the needle 10 is retracted in the direction of being withdrawn from the implant site Sk. As a result, the transplanted Tg is placed in the space where the vicinity of the tip of the needle-shaped portion 10 was located inside the transplanted site Sk, so that when the transplanted Tg exits the needle-shaped portion 10, the surrounding tissue It is suppressed that the cells are pressed and loaded.

Then, as shown in FIG. 17, the rod 30 is withdrawn from the transplant Tg. The transplant Tg attaches to the surrounding tissue and remains inside the transplant site Sk. Here, before the rod-shaped body 30 is pulled out, the transplanted product Tg held in the rod-shaped body 30 is exposed from the opening 11 to the inside of the transplantation site Sk for a predetermined time as shown in FIG. It is preferable to keep it. The predetermined time is, for example, 0.5 seconds or more. The tissue inside the transplant site Sk is under high pressure due to the tightly packed cells, and over time, the tissue around the transplant Tg is filled with the tissue. At this time, the needle-shaped portion 10 may be retracted to a position where the entire needle-shaped portion 10 comes out of the transplantation site Sk, or a part of the needle-shaped portion 10 remains stuck in the transplantation site. May be good. When the entire needle-shaped portion 10 is ejected from the transplantation site Sk, the time required for the tissue to fill the periphery of the transplantation Tg is shorter.

By filling the periphery of the transplant Tg with the tissue inside the transplant site Sk, the movement of the position of the transplant Tg is suppressed when the rod 30 is withdrawn from the transplant Tg. As a result, the transplant Tg is placed in the target area for transplantation inside the transplant site Sk, and the transplantation of the transplant Tg is completed.

In the cell transplantation apparatus 100 of the present embodiment, the transplantation Tg is housed in the needle-shaped portion 10 in a state where the rod-shaped body 30 is stuck in the transplantation Tg. Therefore, inside the needle-shaped portion 10, the orientation of the transplanted Tg with respect to the needle-shaped portion 10 is fixed, and when the transplanted Tg contains a plurality of cell group Cg, the positional relationship between the cell group Cg is also fixed. .. Therefore, the rod-shaped body 30 is pierced into the implant-shaped body 30 so that the arrangement of the transplanted Tg with respect to the needle-shaped portion 10 becomes a predetermined arrangement according to the angle of the needle-shaped portion 10 that pierces the transplantation site Sk. By retaining the transplant Tg, the transplant Tg can be transplanted in a predetermined arrangement with respect to the transplant site Sk.

For example, when the transplanted Tg contains a first cell group Cg1 which is a cell mass of epithelial cells and a second cell group Cg2 which is a cell mass of mesenchymal cells and functions as a hair follicle primordia, the first The second cell group Cg2 is located on the side where the tip of the rod 30 is located with respect to the one cell group Cg1, and the transplant Tg is placed on the rod 30 so that the first cell group Cg1 and the second cell group Cg2 are in contact with each other. To hold. Then, the needle-shaped portion 10 is pierced into the transplantation site Sk along a direction orthogonal to the surface of the skin which is the transplantation site Sk, and the transplant Tg is placed inside the transplantation site Sk. As a result, the first cell group Cg1 consisting of epithelial cells is closer to the surface of the skin than the second cell group Cg2 consisting of mesenchymal cells in a state where the first cell group Cg1 and the second cell group Cg2 are in contact with each other. Placed in position. Therefore, the formation of hair follicles from the transplanted Tg is likely to proceed well.

The needle-shaped portion 10 may be pierced into the transplantation site Sk along a direction inclined with respect to the surface of the skin. Again, the first cell group Cg1 is located closer to the surface of the skin than the second cell group Cg2.

Further, in the cell transplantation apparatus 100, after the needle-shaped portion 10 pierces the transplantation site Sk, the needle-shaped portion 10 is pulled out to a position where the transplant Tg held in the rod-shaped body 30 comes out from the opening 11 for a predetermined time. It may be provided with a pull-out adjustment mechanism for keeping. In other words, the extraction adjusting mechanism keeps the state in which the tip end portion of the rod-shaped body 30 protrudes from the opening 11 of the needle-shaped portion 10 and pierces the living body for a predetermined time.

The pull-out adjustment mechanism may include, for example, a mechanism for pulling out the needle-shaped portion 10 and the rod-shaped body 30 from the living body in this order with a predetermined time difference. A member for pulling out the rod-shaped body 30 from the living body is included. Further, the extraction adjustment mechanism may include a mechanism for stopping the needle-shaped portion 10 directly above the surface of the living body after the needle-shaped portion 10 is pulled out from the living body.

The series of steps included in the method of arranging the implant, that is, the step of piercing the needle-shaped portion 10 into the living body, the step of pulling out the needle-shaped portion 10 from the living body, and the step of pulling out the rod-shaped body 30 from the living body are described above. It may be continuously performed based on the control of the mechanism including the adjusting mechanism and the position changing unit 40. In other words, the series of steps may be performed automatically by mechanical processing and may not require manual intervention. Alternatively, inter-process or a part of the process may be performed manually.

[Modification example]
Hereinafter, a modified example of the cell transplantation device 100 of the first embodiment will be described.
<Stopper part>
As shown in FIG. 18, the cell transplantation device 100 may include a stopper portion 31. The stopper portion 31 projects from the rod-shaped body 30 along the radial direction of the rod-shaped body 30. The stopper portion 31 has a function of suppressing the movement of the cell group Cg pierced by the rod-shaped body 30 toward the base end portion of the rod-shaped body 30.

The shape of the stopper portion 31 is not particularly limited as long as the stopper portion 31 projects from the rod-shaped body 30 to such an extent that the movement of the cell group Cg can be suppressed. For example, the stopper portion 31 may have a disk shape. .. The outer diameter do3 of the stopper portion 31 is smaller than the inner diameter di1 of the needle-shaped portion 10, and the entire stopper portion 31 is inside the needle-shaped portion 10 in a state where the tip portion of the rod-shaped body 30 is located inside the needle-shaped portion 10. Located in.

As described above, when the cell group Cg is a cell mass and the transplant contributes to hair growth or hair growth, the diameter of the cell group Cg is about 0.1 mm or more and 1 mm or less. In this case, as described above, the outer diameter do2 of the rod-shaped body 30 is selected from the range of, for example, 10 μm or more and 250 μm or less, and the inner diameter di1 of the needle-shaped portion 10 is, for example, the range of 0.2 mm or more and 1.5 mm or less. Is selected from. The outer diameter do3 of the stopper portion 31 is selected from, for example, a range of 50 μm or more and 1.1 mm or less.

In one example, when the diameter of the cell group Cg is about 0.1 mm to 0.2 mm, the outer diameter do2 of the rod-shaped body 30 is 50 μm, the inner diameter di1 of the needle-shaped portion 10 is 0.22 mm, and the outer diameter of the needle-shaped portion 10 is 0.22 mm. The do1 is 0.4 mm, and the outer diameter do3 of the stopper portion 31 is 0.2 mm. In this case, a 27G injection needle may be used as the needle-shaped portion 10.

In another example, when the diameter of the cell group Cg is about 0.2 mm to 0.3 mm, the outer diameter do2 of the rod-shaped body 30 is 100 μm, the inner diameter di1 of the needle-shaped portion 10 is 0.4 mm, and the needle-shaped portion 10 is formed. The outer diameter do1 is 0.5 mm, and the outer diameter do3 of the stopper portion 31 is 0.37 mm. In this case, a 25G injection needle may be used as the needle-shaped portion 10.

As shown in FIG. 19, when the rod-shaped body 30 pierces the cell group Cg, the cell group Cg is arranged between the stopper portion 31 and the tip of the rod-shaped body 30. When the cell group Cg tries to move toward the proximal end portion of the rod-shaped body 30, the cell group Cg hits the stopper portion 31 and the movement of the cell group Cg is suppressed.

For example, when the cell group Cg has a size that is in contact with the inner surface of the needle-shaped portion 10, the needle-shaped portion 10 is pierced into a living body while the cell group Cg is housed, and then only the needle-shaped portion 10 is pulled out. Occasionally, friction may occur between the inner surface of the needle-shaped portion 10 and the cell group Cg, and the cell group Cg may try to move together with the needle-shaped portion 10. In such a case, the movement of the cell group Cg is stopped by the stopper portion 31, so that the cell group Cg is suppressed from coming out of the target region of transplantation together with the needle-shaped portion 10.

Further, when the cell group Cg is delivered from the holding portion 60 of the cell accommodating assisting device 110 to the rod-shaped body 30, the cell group Cg is arranged at a position closer to the base end portion of the rod-shaped body 30 than at a desired position. Is suppressed.

As shown in FIG. 20, the stopper portion 31 may not be provided in the entire circumferential direction of the rod-shaped body 30, and may project from a part of the circumferential direction of the rod-shaped body 30. In short, it is sufficient that the stopper portion 31 hits the cell group Cg to suppress the movement of the cell group Cg. Within the range in which the movement of the cell group Cg is suppressed, the smaller the stopper portion 31, the smaller the resistance when the rod-shaped body 30 is pulled out from the living body.

<Non-adsorption treatment>
At least one of the inner surface of the needle-shaped portion 10, the surface of the rod-shaped body 30, and the tip surface of the holding portion 60 is subjected to a non-adsorption treatment, which is a treatment for suppressing adsorption of cell group Cg to these surfaces. It may be applied. As described above, the needle-shaped portion 10, the rod-shaped body 30, and the holding portion 60 are formed of a metal or a resin, but the cell group Cg may be easily adsorbed on the surface made of these materials. Since the non-adsorption treatment is performed, the cell group Cg is suppressed from being adsorbed to the needle-shaped portion 10, the rod-shaped body 30, and the holding portion 60, so that the cell group Cg is accommodated in the needle-shaped portion 10. The release of the retention of the cell group Cg by the holding portion 60 and the extraction of the needle-shaped portion 10 and the rod-shaped body 30 at the time of arranging the cell group Cg in the living body proceed smoothly.

The non-adsorption treatment is, for example, a coating of a polymer material having an effect of suppressing adsorption of a biological substance such as a protein, or a surface hydrophilization treatment by plasma irradiation. As the polymer material, for example, polyethylene glycol, Pluronic F-127 (manufactured by Merck & Co., Ltd.), Prevelex (manufactured by Nissan Chemical Industries, Ltd.), Blockmaster (manufactured by JSR Life Science Co., Ltd.) and the like can be used.
In the rod-shaped body 30, it is sufficient that at least the surface of the portion holding the cell group Cg is subjected to the non-adsorption treatment.

<Multiple needle-shaped parts>
The number of needle-shaped portions 10 included in the cell transplantation device 100 is not particularly limited. As shown in FIG. 21, the cell transplantation device 100 may include a plurality of needle-shaped portions 10. By providing the cell transplantation device 100 with a plurality of needle-shaped portions 10, a plurality of transplants Tg can be transplanted together. The arrangement of the plurality of needle-shaped portions 10 is not particularly limited, and the plurality of needle-shaped portions 10 may be arranged regularly or irregularly.

When the cell transplantation device 100 includes a plurality of needle-shaped portions 10, a rod-shaped body 30 is provided for each needle-shaped portion 10. The movement of the rod-shaped body 30 with respect to the needle-shaped portion 10 may be performed collectively for the plurality of needle-shaped portions 10 and the rod-shaped body 30, or may be performed separately for each pair of the needle-shaped portion 10 and the rod-shaped body 30. You may.

When accommodating the cell group Cg in the plurality of needle-shaped portions 10, one holding portion 60 of the cell accommodating assisting device 110 sequentially transfers the cell group Cg to the rod-shaped body 30 for the plurality of rod-shaped bodies 30. Thereby, the cell group Cg may be sequentially accommodated in the plurality of needle-shaped portions 10. Alternatively, the cell containment assisting device 110 includes a plurality of holding portions 60, and each holding portion 60 delivers the cell group Cg to each different rod-shaped body 30, whereby the cell group Cg is accommodated in each needle-shaped portion 10. May be done in parallel. The plurality of holding portions 60 may be moved separately or collectively.

In FIG. 21, a partition wall 21 is provided between the needle-shaped portion 10 and the support portion 20, and the rod-shaped body 30 penetrates the partition wall 21. However, the partition wall 21 is not provided. The space inside the needle-shaped portion 10 may communicate with the space inside the support portion 20.

As described above, according to the first embodiment, the effects listed below can be obtained.
(1) The implant Tg is housed in the needle-shaped portion 10 in a state of being pierced by the rod-shaped body 30. Therefore, inside the needle-shaped portion 10, the orientation of the transplanted Tg with respect to the needle-shaped portion 10 is fixed, and when the transplanted Tg contains a plurality of cell group Cg, the positional relationship between the cell group Cg is also fixed. .. Therefore, it is possible to transplant the transplant Tg into the tissue in the living body with a predetermined arrangement, and it is possible to control the arrangement of the transplant Tg in the tissue of the transplant destination.

(2) Since the tip of the rod-shaped body 30 is sharp, the rod-shaped body 30 can easily be pierced by the transplanted Tg, so that the transplanted Tg can be smoothly accommodated in the needle-shaped portion 10.
(3) Since the outer diameter do2 of the rod-shaped body 30 is 0.4 times or less the inner diameter di1 of the needle-shaped portion 10, the transplant Tg is placed between the rod-shaped body 30 and the inner surface of the needle-shaped portion 10. Sufficient space is secured for accommodation. Therefore, the implant Tg can be smoothly accommodated in the needle-shaped portion 10. In addition, it is possible to suppress the load on the cell group Cg when it is contained in the needle-shaped portion 10.

(4) The cell transplantation device 100 includes a mechanism for keeping the tip of the rod-shaped body 30 protruding from the opening 11 of the needle-shaped portion 10 and piercing the living body. As a result, the state in which the transplant Tg pierced by the rod-shaped body 30 is arranged in the living body is maintained. Therefore, with the passage of time, the tissue in the living body fills the circumference of the transplant Tg. As a result, when the rod-shaped body 30 is pulled out, the transplanted Tg is suppressed by the surrounding tissue, so that the transplanted Tg is suppressed from moving together with the rod-shaped body 30.

(5) If at least one of the inner surface of the needle-shaped portion 10, the surface of the rod-shaped body 30, and the tip surface of the holding portion 60 is a surface subjected to the non-adsorption treatment of cells, a transplant is made from these surfaces. Tg is easy to separate. Therefore, it is possible to smoothly release the retention of the cell group Cg by the holding portion 60 and to smoothly pull out the needle-shaped portion 10 and the rod-shaped body 30 when arranging the transplanted Tg in the living body.

(6) When the cell transplantation device 100 includes the stopper portion 31, the transplant Tg moves toward the base end portion of the rod-shaped body 30 when the rod-shaped body 30 is moved with respect to the needle-shaped portion 10. Is suppressed.

(7) The cell accommodating unit 120 faces the tip of the holding portion 60 and the tip of the rod-shaped body 30, and is inserted into the holding portion 60 until the tip of the rod-shaped body 30 is inserted into the holding portion 60. On the other hand, a moving mechanism unit for relatively moving the rod-shaped body 30 is provided. As a result, the rod-shaped body 30 pierces the cell group Cg held in the holding portion 60, and the cell group Cg is delivered from the holding portion 60 to the rod-shaped body 30. According to such a configuration, since the movement of the cell group Cg is suppressed by the holding portion 60, the rod-shaped body 30 is likely to be pierced by the cell group Cg. Therefore, as compared with accommodating the cell group Cg in the needle-shaped portion 10 using tweezers or the like, the rod-shaped body 30 can accurately hold the cell group Cg. In addition, it is possible to reduce the load on the cell group Cg as compared with carrying the cell group Cg by sandwiching it as in the case of using tweezers.

(8) The moving mechanism unit moves from a holding position for holding the cell group Cg arranged in the tray 130 to a storage position where the tip portion of the holding portion 60 and the tip portion of the rod-shaped body 30 face each other. , The position of the holding portion 60 is changed. As a result, the cell group Cg is held by the holding portion 60 and carried from the tray 130 to the rod-shaped body 30, so that the cell group Cg is smoothly contained in the needle-shaped portion 10.

(9) When the tip of the rod 30 is inserted into the holding portion 60, if the tip of the rod 30 is located inside the needle 10, the cell group Cg is accommodated in the needle 10. , The time that the cell group Cg is exposed to the outside air can be shortened. Therefore, it is possible to protect the cell group Cg.

(10) When the tip of the rod-shaped body 30 is inserted into the holding portion 60, if the tip of the rod-shaped body 30 protrudes from the opening 11 of the needle-shaped portion 10, the outer diameter of the holding portion 60 does not matter. , The cell group Cg can be transferred from the holding portion 60 to the rod-shaped body 30. Therefore, since the degree of freedom regarding the thickness of the holding portion 60 is increased, the thickness of the holding portion 60 can be set to a thickness more suitable for holding the cell group Cg or a thickness that is easy to form.

(11) The method for accommodating the transplanted Tg includes that the rod-shaped body 30 pierces the cell group Cg and that the cell group Cg is inserted into the needle-shaped portion 10 through the opening 11 of the needle-shaped portion 10. As a result, the implant Tg is housed in the needle-shaped portion 10 in a state of being pierced by the rod-shaped body 30. Therefore, the transplant Tg can be transplanted to the tissue in the living body in a predetermined arrangement.

(12) The method for accommodating the transplanted Tg is that the rod-shaped body 30 pierces the first cell group Cg1 and then pierces the second cell group Cg2, and the second cell group Cg2 is pierced from the opening 11 of the needle-shaped portion 10. Includes being placed in the needle-shaped portion 10. As a result, the transplant Tg containing these cell groups Cg is housed in the needle-shaped portion 10 in a state where the rod-shaped body 30 is stuck in the two cell groups Cg. Therefore, the arrangement of the transplanted product Tg in the tissue of the transplant destination can be controlled including the positional relationship between the cell groups Cg.

(13) The method of arranging the transplant Tg is to pierce the living body with the needle-shaped portion 10 containing the transplant Tg pierced by the rod-shaped body 30, and to leave the transplant Tg in the living body to from the living body to the needle-shaped portion 10. Including pulling out. As a result, the orientation of the transplant Tg in the needle-shaped portion 10 and the positional relationship between the cell groups Cg are reflected in the arrangement of the transplant Tg in the tissue of the transplant destination. Therefore, it is possible to control the placement of the transplant Tg in the tissue of the transplant destination.

(14) The method of arranging the transplant Tg is such that the needle-shaped portion 10 is pulled out from the living body until the transplanted Tg pierced by the rod-shaped body 30 comes out from the opening 11 of the needle-shaped portion 10, and then the rod-shaped portion 10 is arranged. Includes withdrawing body 30 from the transplant Tg. As a result, with the passage of time, the tissue in the living body fills the circumference of the transplant Tg. As a result, when the rod-shaped body 30 is pulled out, the transplanted Tg is suppressed by the surrounding tissue, so that the transplanted Tg is suppressed from moving together with the rod-shaped body 30.

(Second Embodiment)
With reference to FIGS. 22 and 23, a second embodiment of the cell transplant device, the cell storage unit, the method of containing the transplant, and the method of arranging the transplant will be described. The cell transplantation apparatus of the second embodiment is also used for transplantation of the same transplant as the first embodiment. Hereinafter, the differences between the second embodiment and the first embodiment will be mainly described, and the same reference numerals will be given to the same configurations as those of the first embodiment, and the description thereof will be omitted.

In the second embodiment, the portion of the rod-shaped body 30 holding the transplant Tg is left in the living body.
As shown in FIG. 22, the cell transplantation device 101 of the second embodiment has the same configuration as the cell transplantation device 100 of the first embodiment, and has a dividing portion which is a mechanism for dividing the rod-shaped body 30. It has 50. The dividing portion 50 includes, for example, a cutting blade 51 and a cutting mechanism portion 52 that causes the cutting blade 51 to perform an operation for cutting the rod-shaped body 30.

As long as the rod-shaped body 30 can be cut, the structure and shape of the cutting blade 51 are not limited. For example, the cutting blade 51 has a scissors shape that sandwiches and cuts the rod-shaped body 30. The cutting blade 51 is arranged outside the needle-shaped portion 10, for example.

The cutting mechanism portion 52 includes a member for transmitting power to the cutting blade 51. The cutting mechanism 52 may be operated manually, or the cutting mechanism 52 may include an electronic component such as a motor and the cutting mechanism 52 may be operated by electrical control. ..

The cell accommodating unit 120 of the second embodiment includes a cell transplanting device 101 and a cell accommodating assisting device 110 having the same configuration as that of the first embodiment, and the method of accommodating the transplant is the same as that of the first embodiment. It is done in.

In the method of arranging the transplanted product of the second embodiment, as in the first embodiment, after the transplantation site Sk is stabbed by the needle-shaped portion 10, only the needle-shaped portion 10 is withdrawn from the transplantation site Sk. As a result, as shown in FIG. 23, the transplant Tg held in the rod-shaped body 30 is arranged inside the transplantation site Sk, and the rod-shaped body 30 is located between the surface of the transplantation site Sk and the opening 11 of the needle-shaped portion 10. Is exposed. Then, by moving the cutting blade 51, the rod-shaped body 30 is cut between the surface of the transplantation site Sk and the opening 11. As a result, the detached portion 35 including the tip portion of the rod-shaped body 30 is separated from the other portion of the rod-shaped body 30, and the transplanted Tg is placed in the living body in a state where the detached portion 35 is stuck in the transplanted Tg. ..

The cutting blade 51 is configured to be movable with respect to the needle-shaped portion 10, and when the implant Tg is housed in the needle-shaped portion 10 or when the needle-shaped portion 10 pierces the transplantation site Sk. The cutting blade 51 may be separated from the needle-shaped portion 10. Further, the method of dividing the rod-shaped body 30 is not limited to cutting by the cutting blade 51, and the dividing portion 50 may be provided with a mechanism for separating the detached portion 35 from the portion of the rod-shaped body 30 other than the detached portion 35. Further, the rod-shaped body 30 may be divided inside the needle-shaped portion 10 or the support portion 20.

As described above, in the second embodiment, when the transplant Tg is placed in the living body, the rod-shaped body 30 is not pulled out from the transplant Tg, and the detached portion 35 including the portion of the rod-shaped body 30 stuck in the transplant Tg is provided. , Left in vivo with the transplant Tg.

Therefore, since it is not necessary to withdraw the rod-shaped body 30 from the living body and the transplanted Tg, it is possible to suppress the movement of the transplanted Tg in the living body due to the withdrawal of the rod-shaped body 30. Therefore, it is possible to more accurately control the orientation and depth of the arrangement of the transplant Tg by controlling the orientation of the transplant Tg in the needle-shaped portion 10 and controlling the depth at which the needle-shaped portion 10 is pierced into the living body. can.

Further, the detached portion 35 left in the living body can be made to function as a member for inducing tissue formation from the transplant Tg. Inside the transplant site Sk, the withdrawal portion 35 extends from the transplant Tg toward the surface of the transplant site Sk, and the end of the withdrawal portion 35 protrudes from the surface of the transplant site Sk. This induces tissue formation along the detachment portion 35. For example, when the transplant Tg contains a hair follicle primordium, tissue formation can be induced so that the hair follicle is formed to the surface layer of the skin and the formed hair goes out of the skin. Therefore, it is possible to prevent the formed hair from being buried inside the skin, and the result of cell transplantation can be obtained well.

The cell transplantation device 101 of the second embodiment may also include a stopper portion 31 or a plurality of needle-shaped portions 10 and a plurality of rod-shaped bodies 30 as in the modified example of the first embodiment. You may.

In the second embodiment, at least the detached portion 35 of the rod-shaped body 30 is formed from a biocompatible material. Examples of biocompatible materials include silicone, polystyrene, PLA (polylactide), PGA (polyglycolide), PCL (polycaprolactone), polyethylene, polypropylene, PLGA (polylactide-glycolide copolymer), and PDS (polydioxanone). , PEG (polyethylene glycol), ethylene, vinyl acetate copolymer, poly2-ethyl-2-oxazoline, poly2-methyl-2-oxazoline, PHB (polyhydroxybutyric acid), PBS (polycaprolactone butylene), LCL (poly) Glactin polycaprolactone copolymer), polyglycolic acid lactic acid copolymer, biodegradable polyurethane, polyglycolic acid, apatite, PEEK (polyether ether ketone), carboxyvinyl polymer, dextran, dextrin, starch, cellulose, hydroxypropyl Cellulose, hyaluronic acid, chitin, chitosan, pectic acid, galactan, collagen, fibronectin, laminin, proteoglycan, vitronectin, fibronectin, serum albumin, heparin, entactin, tenacin, thrombospontin, purulan, pectin, atelocollagen, gelatin, hydroxyapatite, Selected from the group consisting of chondroitin sulfate, leozane, xanthan gum, gazein, sodium chondroitin sulfate, polyvinylpyrrolidone, phenylalanine, tyrosine, isoleucine, polynucleotide, cytochrome C, β-tricalcium phosphate, sodium alginate, and N-isopropylacrylamide. 1 or more can be used.

The detachment portion 35 may be formed of a biocompatible material that dissolves in the living body. For example, the detached portion 35 is formed of a water-soluble material, and the detached portion 35 is dissolved by the water contained in the living tissue. According to such a configuration, the detached portion 35 disappears with the passage of time in the living body, so that it is not necessary to remove the detached portion 35.

Furthermore, when the detached portion 35 is formed of a material that dissolves in the living body, the rod-shaped body 30 may not be divided, especially when the time required for the detached portion 35 to dissolve is short. .. After the implant Tg and the detached portion 35 of the rod-shaped body 30 are released from the needle-shaped portion 10 into the living body, the detached portion 35 dissolves in the living body over time even if the rod-shaped body 30 is not divided. Thereby, the portion of the rod-shaped body 30 other than the detaching portion 35 can be separated from the detaching portion 35. As a result, the cell transplantation device 101 can be removed from the surface of the living body, leaving the transplanted product Tg. In this case, the effect of inducing tissue formation by the detached portion 35 is small, but as described above, the effect of suppressing the movement of the transplant Tg in the living body due to the withdrawal of the rod-shaped body 30 can be obtained.

For example, the entire rod-shaped body 30 may be formed of a material that dissolves in the living body, and in this case, the portion of the rod-shaped body 30 stuck in the living body dissolves. This melting portion is the detaching portion 35. When the rod-shaped body 30 is not divided, the cell transplantation device 101 may not include the division portion 50.

In the second embodiment, the portion of the rod-shaped body 30 that retains the cell group Cg may be coated with a substance that promotes cell adhesion. In other words, the detachment portion 35 may have the coated surface. As a result, the retention of the cell group Cg by the rod-shaped body 30 is stable, and the position of the cell group Cg is suppressed from being displaced due to vibration or the like when the needle-shaped portion 10 pierces the living body.

As the substance that promotes cell attachment, for example, one or more selected from the group consisting of gelatin, collagen, and laminin can be used.
As described above, according to the second embodiment, the following effects can be obtained in addition to the effects of (1) to (3) and (6) to (13) of the first embodiment.

(15) The detaching portion 35 of the rod-shaped body 30 is configured to be able to be separated from a portion other than the detaching portion 35 of the rod-shaped body 30 in a state where the rod-shaped body 30 is stuck in the living body. According to such a configuration, the placement of the transplant Tg in the living body can be completed without pulling out the rod-shaped body 30 from the transplant Tg. Therefore, the transplant Tg is suppressed from moving when the rod-shaped body 30 is pulled out. In addition, the detached portion 35 can be made to function as a member for inducing tissue formation from the transplant Tg.

(16) If the cell transplanting device 101 is provided with a dividing portion 50 which is a mechanism for separating the detaching portion 35 from a portion other than the detaching portion 35 in the rod-shaped body 30, the separating portion 35 can be accurately separated. be.

(17) Since the detaching portion 35 is formed of a material that dissolves in the living body, it is not necessary to remove the detaching portion 35 from the living body, so that convenience is enhanced. Further, the detaching portion 35 can be separated from the other portion of the rod-shaped body 30 without providing a mechanism for separating the detaching portion 35.

(18) If the detachment portion 35 has a surface coated with a substance that promotes cell adhesion, the retention of the transplanted Tg in the detachment portion 35 is stable, and therefore, when the needle-shaped portion 10 pierces the living body. It is possible to prevent the position of the transplanted Tg from being displaced due to vibration or the like.

(Example)
The above-mentioned cell transplantation apparatus will be described with reference to specific examples.
A cell transplantation device was prepared by using a 25 G injection needle as a needle-shaped portion and a fine needle as a rod-shaped body. The inner diameter of the needle-shaped portion is 0.40 mm, and the outer diameter of the needle-shaped portion is 0.50 mm. The outer diameter of the rod-shaped body is 0.10 mm. In addition, a cell containment assisting device was manufactured using a precision pipe as a holding part. The inner diameter of the holding portion is 0.17 mm, and the outer diameter of the holding portion is 0.36 mm.

The inside of the holding part was sucked by the pump mechanism constituting the suction part to hold the cell mass at the tip of the holding part, and the holding part was inserted into the needle-shaped part so that the rod-shaped body in the needle-shaped part pierced the cell group. After that, it was confirmed that the cell group was retained in the rod-shaped body in the needle-shaped portion by stopping the suction and pulling out the holding portion from the needle-shaped portion.

Then, the needle-shaped part was pierced into the removed skin of the nude mouse, and only the needle-shaped part was pulled out from the removed skin, and after maintaining this state for 0.5 seconds, the rod-shaped body was pulled out from the removed skin. As a result, a cell mass was placed inside the excised skin.

(Modification example)
Each of the above embodiments can be modified and implemented as follows.
-When the transplanted Tg contains a hair follicle primordium, one cell group Cg may function as a hair follicle primordium by having an aggregated portion of mesenchymal cells and an aggregated portion of epithelial cells. .. Such a cell group Cg can be obtained, for example, by mixing and culturing mesenchymal cells and epithelial cells under predetermined conditions. When the hair follicle primordium consisting of one cell group Cg is housed in the needle-shaped portion 10, the aggregated portion of the mesenchymal cells is on the side where the tip of the rod 30 is located with respect to the aggregated portion of the epithelial cells. The rod-shaped body 30 is made to hold the cell group Cg so as to be arranged in. As a result, when the cell group Cg is placed inside the skin by piercing the skin with the needle-shaped portion 10, the aggregated portion of epithelial cells is placed closer to the surface of the skin than the aggregated portion of mesenchymal cells. Will be done.

-Accommodation of the transplant Tg in the needle-shaped portion 10 may be performed without using the cell accommodation assisting device 110. For example, the cell group Cg is picked up with a tweezers, the cell group Cg is pierced by a rod-shaped body 30 protruding from the needle-shaped portion 10, and then the rod-shaped body 30 is pulled into the needle-shaped portion 10 to needle the cell group Cg. It may be housed in the shape portion 10.

Cg ... Cell group Tg ... Transplant 10 ... Needle-shaped part 11 ... Opening 20 ... Support part 30 ... Rod-shaped body 31 ... Stopper part 35 ... Detachment part 40 ... Position change part 50 ... Dividing part 51 ... Cutting blade 52 ... Cutting mechanism part 60 ... Holding unit 70 ... Arrangement changing unit 80 ... Suction unit 100, 101 ... Cell transplanting device 110 ... Cell storage assisting device 120 ... Cell storage unit 130 ... Tray 131 ... Recess

Claims (20)

The needle-shaped portion extending in a cylindrical shape and having an opening at the tip of the needle-shaped portion, and the needle-shaped portion.
The rod-shaped body extending inside the needle-shaped portion along the extending direction of the needle-shaped portion, and having a tip portion capable of piercing a transplant containing a cell group to be transplanted into a living body. With a rod-shaped body,
The rod-shaped body has the needle-like shape between a position where the tip portion of the rod-shaped body is arranged inside the needle-shaped portion and a position where the tip portion of the rod-shaped body protrudes from the opening of the needle-shaped portion. A cell transplantation device that is configured to be relatively mobile relative to the body. The cell transplantation apparatus according to claim 1, wherein the tip of the rod-shaped body is sharp. The cell transplantation apparatus according to claim 1 or 2, wherein the outer diameter of the rod-shaped body is 0.4 times or less the inner diameter of the needle-shaped portion. The cell transplantation apparatus according to any one of claims 1 to 3, further comprising a mechanism for keeping the tip of the rod-shaped body protruding from the opening of the needle-shaped body to pierce the living body. A stopper portion protruding from the rod-shaped body is provided.
The cell transplanting apparatus according to any one of claims 1 to 4, wherein the stopper portion has a function of suppressing the movement of the transplant toward the base end portion of the rod-shaped body. The cell transplantation apparatus according to any one of claims 1 to 5, wherein at least one of the inner surface of the needle-shaped portion and the surface of the rod-shaped body is a surface subjected to a non-adsorption treatment of cells. The rod-shaped body has a detaching portion including a tip portion of the rod-shaped body.
The detached portion according to any one of claims 1 to 5, wherein the detached portion can be separated from a portion of the rod-shaped body other than the detached portion while the tip end portion of the rod-shaped body is stuck in the living body. The cell transplant device described. The cell transplantation apparatus according to claim 7, further comprising a mechanism for separating the detached portion from a portion of the rod-shaped body other than the detached portion. The cell transplantation apparatus according to claim 7 or 8, wherein the detached portion is formed of a material that dissolves in a living body. The cell transplantation apparatus according to any one of claims 7 to 9, wherein the detached portion has a surface coated with a substance that promotes cell adhesion. A cell containment unit equipped with a cell transplantation device and a cell containment assisting device.
The cell transplantation device is
The needle-shaped portion extending in a cylindrical shape and having an opening at the tip of the needle-shaped portion, and the needle-shaped portion.
The rod-shaped body extending inside the needle-shaped portion along the extending direction of the needle-shaped portion, and having a tip portion capable of piercing a transplant containing a cell group to be transplanted into a living body. With a rod-shaped body,
The rod-shaped body has the needle-like shape between a position where the tip portion of the rod-shaped body is arranged inside the needle-shaped portion and a position where the tip portion of the rod-shaped body protrudes from the opening of the needle-shaped portion. It is configured to be relatively movable with respect to the part,
The cell containment assisting device is
A holding part that extends in a cylindrical shape and
A suction portion for sucking the inside of the holding portion is provided.
The holding portion is configured to be able to hold the cell group at the tip end portion of the holding portion by suction of the suction portion.
The cell accommodating unit faces the tip of the holding portion and the tip of the rod-shaped body, and has the rod-shaped shape with respect to the holding portion until the tip of the rod-shaped body is inserted into the holding portion. A cell-containing unit equipped with a movement mechanism that moves the body relatively. The movement mechanism portion is located at a position where the holding portion holds the cell group arranged on the tray, and the holding portion is located at a position where the tip portion of the holding portion and the tip portion of the rod-shaped body face each other. The cell containing unit according to claim 11. The cell containing unit according to claim 11 or 12, wherein when the tip of the rod is inserted into the holding portion, the tip of the rod is located inside the needle. The cell containing unit according to claim 11 or 12, wherein when the tip of the rod is inserted into the holding portion, the tip of the rod protrudes from the opening of the needle. A method of accommodating a transplant containing a group of cells to be transplanted into a living body in a cell transplant device.
The cell transplantation device is
The needle-shaped portion extending in a cylindrical shape and having an opening at the tip of the needle-shaped portion, and the needle-shaped portion.
A rod-shaped body extending in the extending direction of the needle-shaped portion inside the needle-shaped portion is provided.
The rod-shaped body has the needle-like shape between a position where the tip portion of the rod-shaped body is arranged inside the needle-shaped portion and a position where the tip portion of the rod-shaped body protrudes from the opening of the needle-shaped portion. It is configured to be relatively movable with respect to the part,
The tip of the rod-shaped body pierces the cell group,
The cell group is put into the needle-shaped portion through the opening of the needle-shaped portion, and
How to contain the transplant, including. The cell group is the first cell group and
The transplant comprises the first cell group and the second cell group.
The tip of the rod-shaped body pierces the first cell group and then pierces the second cell group.
The method for accommodating a transplant according to claim 15, wherein the second cell group is put into the needle-shaped portion through the opening of the needle-shaped portion. The method for accommodating a transplant according to claim 15 or 16, wherein the tip portion of the rod-shaped body pierces the cell group held by the tip portion of the holding portion extending in a tubular shape. It is a method of arranging a transplant containing a cell group in a living body from a cell transplant device.
The cell transplantation device is
The needle-shaped portion extending in a cylindrical shape and having an opening at the tip of the needle-shaped portion, and the needle-shaped portion.
A rod-shaped body extending in the extending direction of the needle-shaped portion inside the needle-shaped portion is provided.
The rod-shaped body has the needle-like shape between a position where the tip portion of the rod-shaped body is arranged inside the needle-shaped portion and a position where the tip portion of the rod-shaped body protrudes from the opening of the needle-shaped portion. It is configured to be relatively movable with respect to the part,
To pierce the living body with the needle-shaped portion containing the transplant that was pierced by the rod-shaped body.
By leaving the transplant in the living body and pulling out the needle-shaped portion from the living body,
How to place the transplant, including. After keeping the state in which the needle-shaped portion is pulled out from the living body until the implant pierced by the rod-shaped body comes out from the opening of the needle-shaped portion, the rod-shaped body is pulled out from the transplanted body. The method for arranging a transplant according to claim 18. The method for arranging a transplant according to claim 18, wherein after the needle-shaped portion is stabbed into a living body, the portion of the rod-shaped body in which the transplanted product is pierced is separated from the other portion of the rod-shaped body.

Images