JP2021129702A - Cell transplantation device - Google Patents

Abstract

To provide a cell transplantation device capable of delivering a cell group and substances other than the cell group into an organism.SOLUTION: A cell transplantation device 100 is configured to dispose a cell group in an object area in an organism. The cell transplantation device 100 comprises: a tubular needle-like part 20 extending along one direction; and a plurality of inner tube parts 30 positioned inside the needle-like part 20. The inner tube parts 30 include a first inner tube part for transporting the cell group and a second inner tube part for transporting substances other than the cell group.SELECTED DRAWING: Figure 1

Description

The present invention relates to a cell transplant device used for cell transplantation.

A technique for transplanting a group of cells into a living body has been developed. 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 this group of cells into the skin. For good hair regeneration, it is desirable that hair follicles having a normal tissue structure and good hair forming ability are formed from the transplanted cell group. Therefore, various studies 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). Further, development of a cell transplantation device, which is a device for transferring a cultured cell group from a culture vessel into a living body, is also underway (see, for example, Patent Document 4). The cell transplantation device is provided with a needle-shaped pointed tubular portion, and the cell group is taken into the inside of the tubular portion from the culture vessel. After the tubular portion pierces the target portion of transplantation such as skin, the cell group is released from the tip of the tubular portion, so that the cell group is arranged in the living body.

International Publication No. 2017/073625 International Publication No. 2012/108069 Japanese Unexamined Patent Publication No. 2008-29331 International Publication No. 2019/064653

By the way, when transplanting a cell group, there is a request to supply a substance other than the cell group to the living body together with the cell group. For example, in order to achieve good expression of the function in the transplanted cell group, it is preferable to supply an auxiliary substance that assists the expression of the function of the cell group in vivo together with the cell group. Auxiliary substances are, for example, nutritional components for cells and substances that assist the establishment of cell groups in a living body. The cell transplantation device can take a protective solution, which is a liquid that protects the cell group in the culture vessel, into the tubular part together with the cell group, and release the protective solution into the living body together with the cell group. However, the amount and components of the protective solution taken up are not always sufficient to enhance the activity of the cell group in the living body. Further, in the cell transplantation device, it is difficult to further take in a substance different from the protective solution into the tubular portion. On the other hand, supplying an auxiliary substance to the living body separately from the cell group using a device different from the cell transplantation device means exchanging the device between the time of transplanting the cell group and the time of supplying the auxiliary substance, and the cells. Since it is necessary to align the transplantation position of the group with the supply position of the auxiliary substance, the work for sending the cell group and the auxiliary substance into the living body becomes complicated.

An object of the present invention is to provide a cell transplantation apparatus capable of delivering a cell group and a substance other than the cell group into a living body.

The cell transplantation device that solves the above problems is a cell transplantation device for arranging a cell group in a target region in a living body, and has a tubular needle-shaped portion extending along one direction and the needle-shaped portion. A plurality of inner cylinders located inside the cell group are provided, and a first inner cylinder portion for transferring the cell group and a substance other than the cell group are transferred to the plurality of inner cylinder portions. A second inner cylinder portion is included.

According to the above configuration, by arranging the cell group in the first inner cylinder portion and arranging the target substance which is a substance other than the cell group in the second inner cylinder portion, the cell group is formed inside one needle-shaped portion. It is possible to take in the target substance and transfer them into the living body. Then, since the cell group and the target substance can be released from one needle-shaped portion, the target substance can be supplied to the vicinity of the region where the cell group is arranged in the living body. Therefore, the cell group and the substance other than the cell group can be easily delivered into the living body.

In the above configuration, the inner cylinder portion has a first state in which the tip portion of the inner cylinder portion is located inside the needle-shaped portion, and the tip portion of the inner cylinder portion is an opening of the tip portion of the needle-shaped portion. It may be configured to be movable relative to the needle-shaped portion with respect to the second state protruding from.

According to the above configuration, the needle-shaped portion can be pierced into the living body in the first state, and the cell group and the target substance can be taken in and released in the second state. Therefore, the delivery of the cell group and the target substance into the living body is smoothly promoted.

In the above configuration, the plurality of inner cylinder portions may be configured to be movable between the first state and the second state for each inner cylinder portion.
According to the above configuration, since a plurality of inner cylinders can be taken in and out one by one from the opening of the needle-shaped portion, the cell group and the target substance can be taken in with a sufficient space around the inner cylinder. And can be released. Therefore, these operations can proceed smoothly.

In the above configuration, the two or more inner cylinder portions may be configured to be movable between the first state and the second state at the same time.
According to the above configuration, control of the movement of the inner cylinder portion becomes simpler as compared with the case where a plurality of inner cylinder portions are moved one by one.

In the above configuration, the cell group is an aggregate of cells, the first inner cylinder portion is connected to a mechanism for sucking the inside of the first inner cylinder portion, and the tip portion of the first inner cylinder portion is connected by the suction. The cell group may be taken into the first inner cylinder portion.

According to the above configuration, it is possible to accurately incorporate an aggregate of cells into the inner cylinder portion, and it is also easy to incorporate a desired number of cell groups into the inner cylinder portion.

In the above configuration, at least one second inner cylinder portion included in the plurality of inner cylinder portions is the second inner cylinder portion for transferring a liquid which is a substance other than the cell group, and the second inner cylinder portion. The substance may be taken into the second inner cylinder portion from the side opposite to the tip end portion of the inner cylinder portion.
According to the above configuration, it is possible to efficiently take in the target substance into the inner cylinder portion by taking advantage of the characteristics of the liquid.

In the above configuration, a plurality of the needle-shaped portions may be provided, and each of the needle-shaped portions may be provided with a plurality of the inner cylinder portions including the first inner cylinder portion and the second inner cylinder portion.
According to the above configuration, it is possible to collectively incorporate a plurality of cell groups and target substances into a cell transplantation device, and to collectively arrange a plurality of cell groups and target substances in a living body, thus improving the efficiency of transplantation. Can be enhanced.

According to the present invention, a cell group and a substance other than the cell group can be delivered in vivo.

The figure which shows the structure of the cell transplantation apparatus about one Embodiment of the cell transplantation apparatus. The figure which shows the state which one inner cylinder part protruded from the needle-like part in the cell transplantation apparatus of one Embodiment. It is a figure which shows the cell transplantation method using the cell transplantation apparatus of one Embodiment, and is the figure which shows the step of taking in a cell group into an inner cylinder part. It is a figure which shows the cell transplantation method using the cell transplantation apparatus of one Embodiment, and is the figure which shows the state which the cell group is housed in the needle-like part together with the inner cylinder part. It is a figure which shows the cell transplantation method using the cell transplantation apparatus of one Embodiment, and is the figure which shows the state which the needle-like part was stabbed in the transplantation site. It is a figure which shows the cell transplantation method using the cell transplantation apparatus of one Embodiment, and is the figure which shows the arrangement process of a cell group. It is a figure which shows the cell transplantation method using the cell transplantation apparatus of one Embodiment, and is the figure which shows the supply process of the auxiliary substance. The figure which shows the structure of the cell transplantation apparatus of a modified example. The figure which shows the state which a plurality of inner cylinders protrude from a needle-like part in the cell transplantation apparatus of a modified example. The figure which shows the structure of the cell transplantation apparatus of a modified example.

An embodiment of the cell transplantation apparatus will be described with reference to FIGS. 1 to 7. The cell transplantation device of the present embodiment is used for transplanting a cell group into a living body and supplying a substance other than the cell group. The target area for transplantation is at least one of the intradermal and subcutaneous areas, or a tissue such as an organ.

[Cell group]
The cell group to be transplanted includes a plurality of 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. Alternatively, the cell group may be composed of a plurality of dispersed cells. Further, the cells constituting the cell group may be undifferentiated cells or cells that have been completely differentiated, and the cell group includes undifferentiated cells and differentiated cells. May be good. The cell group is, for example, a cell mass (spheroid), a primordium, a tissue, an organ, an organoid, a mini-organ, or the like.

The cell group has a function of acting on tissue formation in a living body by being arranged in a target region. The cell group to be transplanted contributes to hair growth or hair growth by being arranged, for example, intradermally or subcutaneously. These cell groups have, for example, the ability to function as a hair follicle organ, the ability to differentiate into a hair follicle organ, the ability to induce or promote the formation of a hair follicle organ, the ability to induce or promote the formation of hair in a hair follicle, and the like. .. In addition, the cell group 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 vascular cells.

Specifically, an example of the cell group to be transplanted in the present embodiment is a hair follicle primordium, which is a primitive hair follicle organ. Hair follicle primordium contains mesenchymal cells and epithelial cells. In the hair follicle organ, mesenchymal cells, the hair papilla cells, induce the differentiation of hair follicle epithelial stem cells, and the hair follicle cells repeat division in the hair follicle formed thereby to form hair. NS. Hair follicle primordium is a group of cells that differentiate into these hair follicle organs.

The hair follicle primordium is, for example, a mixture of mesenchymal cells derived from mesenchymal tissue such as the hair papilla and epithelial cells derived from epithelial tissue located in the bulge region or the base of the hair bulb under predetermined conditions. It is formed by culturing. 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 follicles primordia is not limited, and these cells may be cells derived from the hair follicles organ, or the hair follicles organs. It may be a cell derived from a different organ or a cell derived from a pluripotent stem cell.

[Auxiliary substance]
The auxiliary substance is a substance other than the cell group, and is a substance to be supplied into the living body together with the cell group. The auxiliary substance may be a liquid or a solid.

Auxiliary substances are, for example, substances that assist in the expression of cell group functions. When the cell group is a hair follicle primordium, the auxiliary substance directly or indirectly assists the differentiation of the cell group into the hair follicle organ or the formation of hair in the hair follicle organ. The auxiliary substance may chemically or biologically assist the expression of the function of the cell group depending on the components contained in the auxiliary substance, or assist the expression of the function of the cell group by the structure such as the shape of the auxiliary substance. You may.

The auxiliary substance that assists the expression of the function of the cell group is, for example, an additive containing a component that promotes cell proliferation or differentiation, or fixes the cell group in order to suppress the loss of the cell group from the tissue to be transplanted. Fixing agent, etc. The additives include, for example, cell growth factors, nutritional components, physiologically active substances such as cytokines, extracellular matrix such as collagen, and the like. Further, when the cell group contributes to hair growth or hair growth, it is considered that the favorable progress of pore formation by the action of the cell group is an important factor for good hair regeneration. Therefore, when the cell group to be transplanted is a cell group such as a hair follicle primordium that contributes to hair growth or hair growth, the auxiliary substance may be a member that functions as a guide for the formation of pores.

Further, the auxiliary substance may be a substance that assists the entry or withdrawal of the needle-shaped portion of the cell transplantation device into the living body. Such auxiliary substances are, for example, a substance that suppresses the occurrence of pain due to piercing the needle-shaped portion into the living body, and a lubricant that suppresses friction between the living body and the needle-shaped portion.

[Structure of cell transplantation device]
The configuration of the cell transplantation apparatus will be described with reference to FIGS. 1 and 2.
As shown in FIG. 1, the cell transplantation device 100 includes a tubular needle-shaped portion 20 extending along one direction and a plurality of inner tubular portions 30 located inside the needle-shaped portion 20.

The needle-shaped portion 20 has a needle tip portion 10 and an accommodating portion 15. The needle tip portion 10 and the accommodating portion 15 are arranged along the extending direction of the needle-shaped portion 20, and the internal space of the needle tip portion 10 and the internal space of the accommodating portion 15 communicate with each other.

The needle tip portion 10 includes the tip of the needle-shaped portion 20. The needle tip portion 10 has an opening 11 at the tip end portion. That is, the opening 11 is located at the tip of the needle-shaped portion 20. The shape of the needle tip portion 10 is not particularly limited as long as it has a cylindrical shape such as a cylinder or a square cylinder and the tip portion has an outer shape capable of piercing a site to be transplanted in a living body. The tip of the needle tip 10 has, for example, a shape in which the cylinder is cut diagonally with respect to the extending direction thereof, and is sharp.

The accommodating portion 15 accommodates a plurality of inner cylinder portions 30. The shape of the accommodating portion 15 is not particularly limited as long as it can accommodate a plurality of inner cylinder portions 30. For example, the accommodating portion 15 may have a cylindrical shape or a square tubular shape.

The inner cylinder portion 30 has a tubular shape extending along the extending direction of the needle-shaped portion 20. For example, the inner cylinder portion 30 may have a cylindrical shape or a square cylinder shape. The inner cylinder portion 30 has a function of taking in and releasing a transfer target which is a cell group or an auxiliary substance. Of the plurality of inner cylinders 30, the transfer target of one inner cylinder 30 is a cell group, and the transfer target of the remaining inner cylinder 30 is an auxiliary substance.

The inner cylinder portion 30 includes one first inner cylinder portion which is an inner cylinder portion 30 for transferring a cell group, and one or more second inner cylinder portions which are inner cylinder portions 30 for transferring an auxiliary substance. including. The number of the second inner cylinders is not particularly limited. In the present embodiment, as an example, the cell transplantation apparatus 100 has three inner cylinder portions 30 of the inner cylinder portion 30a which is the first inner cylinder portion and the inner cylinder portion 30b and the inner cylinder portion 30c which are the second cylinder portions. The form to be provided will be described.

In the plurality of inner cylinder portions 30, the shape of the inner cylinder portion 30 may or may not be the same. Further, in the plurality of inner cylinder portions 30, the inner diameter of the inner cylinder portion 30 may or may not be constant. The shape and inner diameter of each inner cylinder portion 30 may be determined according to the transfer target for each inner cylinder portion 30.

The inner diameter of the accommodating portion 15 is larger than the inner diameter of the needle tip portion 10. The accommodating portion 15 has an inner diameter large enough to accommodate all the inner cylinder portions 30 together. The needle tip portion 10 has an inner diameter large enough to allow a plurality of inner cylinder portions 30 to pass through one by one. That is, the inner diameter of the needle tip portion 10 is larger than the maximum inner diameter of the plurality of inner cylinder portions 30.

The cell transplantation device 100 further includes a drive unit 40 and a transfer control unit 41. The drive unit 40 moves a plurality of inner cylinder portions 30 in a direction roughly along the extending direction of the needle-shaped portion 20 for each inner cylinder portion 30. Specifically, the drive unit 40 has a state in which the tip portion of the inner cylinder portion 30 is located inside the needle-shaped portion 20 and a state in which the tip portion of the inner cylinder portion 30 protrudes from the opening 11 of the needle tip portion 10. The inner cylinder portion 30 is moved relative to the needle-shaped portion 20 between the two. FIG. 2 shows a state in which the tip end portion of the inner cylinder portion 30a protrudes from the opening portion 11.

The arrangement of the plurality of inner cylinder portions 30 is not limited as long as the tip portions of the plurality of inner cylinder portions 30 can be taken in and out from the opening 11 one by one. For example, the plurality of inner cylinder portions 30 may be arranged in an annular shape along the circumferential direction of the accommodating portion 15, or may be arranged linearly along the radial direction of the accommodating portion 15.

The drive unit 40 moves the plurality of inner cylinder portions 30 independently of each other, that is, moves each inner cylinder portion 30 separately. For example, the drive unit 40 may be a mechanism that includes parts such as a spring and a pressing member that presses the spring, and moves each inner cylinder portion 30 by interlocking these parts based on a user's operation, a motor, or the like. Each inner cylinder portion 30 may be configured to move by electronic control based on a user's instruction, including the electronic component of the above.

The transfer control unit 41 controls the uptake and release of the transfer target in the inner cylinder unit 30. Specifically, it is preferable that the transfer control unit 41 controls the holding state of the transfer target in the inner cylinder portion 30 by utilizing suction or pressurization in the inner cylinder portion 30.

When the transfer target is other than a liquid, that is, when the transfer target is a member such as a cell group, a solid additive, or a guide, the transfer control unit 41 sucks the inside of the inner cylinder portion 30 to cause the inner cylinder. The transfer target is taken into the inner cylinder portion 30 through the opening at the tip portion of the portion 30. Then, when the transfer control unit 41 pressurizes the inside of the inner cylinder portion 30, the transfer target is released from the opening of the tip portion of the inner cylinder portion 30 and arranged in the living body.

Alternatively, the transfer target may be held outside the tip of the inner cylinder 30 by the transfer control unit 41 sucking the inside of the inner cylinder 30. In this case, the inner diameter of the tip of the inner cylinder 30 is smaller than the diameter of the transfer target, and the transfer target is held by the inner cylinder 30 in a state of being in contact with the tip of the inner cylinder 30. Then, the holding of the transfer target in the inner cylinder portion 30 is released by the stop of suction in the inner cylinder portion 30 by the transfer control unit 41 or the pressurization in the inner cylinder portion 30, and the transfer target is arranged in the living body. NS.

When the transfer target is a liquid, the transfer control unit 41 sends the transfer target into the inner cylinder portion 30 from the side opposite to the tip portion of the inner cylinder portion 30, so that the transfer target is transferred to the inner cylinder portion 30. It is captured. Further, when the transfer control unit 41 pressurizes the inside of the inner cylinder portion 30, the transfer target is released from the opening of the tip portion of the inner cylinder portion 30 and arranged in the living body. The pressurization in the inner cylinder portion 30 may be performed by a pressing member such as a piston, or may be performed by further injecting the same liquid as the transfer target.

Alternatively, the transfer control unit 41 may suck the inside of the inner cylinder portion 30, so that the transfer target may be taken into the inside of the inner cylinder portion 30 from the opening of the tip portion of the inner cylinder portion 30. Then, when the transfer control unit 41 pressurizes the inside of the inner cylinder portion 30, the transfer target is released from the opening of the tip portion of the inner cylinder portion 30 and is arranged in the living body.

The transfer control unit 41 may be, for example, a mechanism that includes parts such as a piston and pressurizes or sucks the inside of the inner cylinder portion 30 by the movement of the parts according to the operation of the user, or an electron such as a motor. It may be configured to pressurize or suck the inside of the inner cylinder portion 30 by electronic control based on a user's instruction including parts.

The materials of the needle-shaped portion 20 and the inner cylinder portion 30 are not particularly limited. The needle-shaped portion 20 is formed of, for example, a metal material such as silicon, stainless steel, titanium, cobalt-chromium alloy, magnesium, or a polymer material such as general-purpose plastic, medical plastic, or cosmetic plastic. Examples of the polymer material include polyethylene, polypropylene, polystyrene, polyamide, polycarbonate, cyclic polyolefin, polylactic acid, polyglycolic acid, polycaprolactone, acrylic, urethane resin, aromatic polyetherketone, epoxy resin, and resins thereof. Examples include the copolymerization material of. Further, the needle-shaped portion 20 may be formed of an ionizing radiation curable material such as polyacrylic or a thermosetting material such as urethane or epoxy. The needle tip portion 10 and the accommodating portion 15 may be formed of the same material or may be formed of different materials.

The inner cylinder portion 30 is formed of, for example, a material exemplified as the material of the needle-shaped portion 20 described above. The needle-shaped portion 20 and the inner cylinder portion 30 may be formed of the same material or may be formed of different materials. Further, the plurality of inner cylinder portions 30 do not have to be all formed of the same material. Further, each of the needle-shaped portion 20 and the inner cylinder portion 30 may be formed by a combination of two or more kinds of materials.

[Porting method]
A method of transplanting a cell group using the cell transplantation device 100 will be described. In the following, as an example, a case where a cell group and two kinds of liquid auxiliary substances are delivered into a living body will be described.

As shown in FIG. 3, before transplantation, the cell group Cg is held in a tray 50 such as a culture vessel together with the protective solution Pl. For example, as shown in FIG. 3, the cell group Cg and the protective liquid Pl are placed in the recess 51 of the tray 50. The holding mode of the cell group Cg and the protective liquid Pl in the tray 50 is not limited to the form in which the cell group Cg and the protective liquid Pl are held in the recess 51, and for example, the cell group Cg and the protective liquid Pl are protected on the plane of the tray 50. The liquid Pl may be arranged. Further, the tray 50 is a container different from the culture container, and the cell group Cg may be transferred from the culture container to the tray 50.

The protective liquid Pl may be any liquid that does not easily inhibit the survival of cells, and is preferably a liquid that has a small effect on the living body when injected into the living body. For example, the protective liquid Pl is a liquid that protects the skin such as physiological saline, petrolatum, and a lotion, or a mixture of these liquids. The protective liquid Pl may contain an additive component such as a nutritional component. When the tray 50 is a culture vessel and the cell group Cg is cultured in the tray 50, the protective liquid Pl may be a medium for culturing cells, or may be a liquid exchanged from the medium. There may be. The liquid containing the cell group Cg and the protective solution Pl can be a low-viscosity fluid or a high-viscosity fluid.

First, the operation of the drive unit 40 moves the inner cylinder portion 30a to which the cell group Cg is to be transferred, and the tip portion of the inner cylinder portion 30a is in a state of protruding from the opening 11 of the needle tip portion 10. Then, the tip of the needle tip 10 and the tip of the inner cylinder 30a are brought close to the cell group Cg in the protective liquid Pl, and the inside of the inner cylinder 30a is sucked by the transfer control unit 41. As a result, the cell group Cg is attracted to the tip of the inner cylinder 30a, and the cell group Cg is taken into the inner cylinder 30a together with the protective liquid Pl from the opening of the tip of the inner cylinder 30a.

After that, as shown in FIG. 4, by moving the inner cylinder portion 30a, the tip portion of the inner cylinder portion 30a is pulled into the needle-shaped portion 20, and along with this, the cell group Cg also becomes the needle-shaped portion 20. It is housed inside. In order to protect the cell group Cg, it is preferable that the cell group Cg is surrounded by the protective solution Pl inside the needle tip portion 10.

The inner cylinder portion 30a may be moved to a position where the tip end portion of the inner cylinder portion 30a is arranged inside the needle-shaped portion 20. As shown in FIG. 4, the tip end portion of the inner cylinder portion 30a may be located inside the needle tip portion 10, or the inner cylinder portion 30a is pulled into the inside of the accommodating portion 15 and the inner cylinder portion 30a is drawn. The tip of the may be located inside the accommodating portion 15.

The cell transplantation device 100 accommodating the cell group Cg is carried to a transplantation site such as a skin Sk in a living body, and as shown in FIG. 5, the needle tip portion 10 is pierced at the transplantation site. At this time, since the tip portion of the inner cylinder portion 30a is located inside the needle-shaped portion 20, the tip portion of the needle tip portion 10 is located at the tip portion of the cell transplantation device 100. Since the tip of the needle tip 10 has a shape that easily sticks into the living body, the cell transplant device 100 can smoothly enter the transplant site. The needle tip portion 10 may enter the transplantation site in a direction orthogonal to the surface of the transplantation site, or may enter the transplantation site in a direction inclined with respect to the surface of the transplantation site.

When the tip of the needle tip 10 enters the target area for transplantation, the inner cylinder 30a is moved so that the tip of the inner cylinder 30a protrudes from the opening 11 of the needle tip 10. Then, as shown in FIG. 6, by pressurizing the inside of the inner cylinder portion 30a, the cell group Cg and the protective liquid Pl are released from the opening of the tip portion of the inner cylinder portion 30a, and the target region for transplantation is formed. Is placed in.

When the tip of the inner cylinder portion 30a is in a state of protruding from the opening 11, the needle-shaped portion 20 is slightly retracted in the direction in which the needle tip portion 10 is pulled out from the transplant site, and the inside of the transplant site is formed. In the space where the tip end portion of the needle tip portion 10 was located, the tip end portion of the inner cylinder portion 30a may be arranged. Then, the cell group Cg may be released into the space where the tip of the needle tip 10 is located. As a result, when the cell group Cg exits the inner cylinder portion 30a, it is suppressed from being pressed by the surrounding tissues and the cell group Cg being loaded.
When the cell group Cg is placed in the target area for transplantation, the inner cylinder portion 30a is moved and pulled into the inside of the containment portion 15.

Subsequently, as shown in FIG. 7, the operation of the drive unit 40 moves the inner cylinder portion 30b to which the auxiliary substance is transferred, and the tip portion of the inner cylinder portion 30b protrudes from the opening 11 of the needle tip portion 10. It is said that it is in a state of being. Then, the transfer control unit 41 pours the additive liquid Sl, which is an auxiliary substance, into the inner cylinder portion 30b from the side opposite to the tip portion of the inner cylinder portion 30b. The additive liquid Sl passes through the inside of the inner cylinder portion 30b and exits from the opening at the tip portion of the inner cylinder portion 30b. As a result, the additive solution Sl is supplied around the cell group Cg arranged in the target region for transplantation. When a predetermined amount of the additive liquid Sl is supplied in the vicinity of the cell group Cg, the supply of the additive liquid Sl to the inner cylinder portion 30b is stopped, and the inner cylinder portion 30b is moved and drawn into the inside of the accommodating portion 15.

Note that FIG. 7 illustrates a form in which the inner cylinder portion 30b protrudes from the opening 11 in a linearly extended state, but the inner cylinder portion 30b has flexibility and is, for example, in the process of movement. It may be taken in and out of the opening 11 while being deformed so as to bend. The same applies to the inner cylinder portions 30a and 30c.

Subsequently, the same operation as the above-mentioned inner cylinder portion 30b is repeated for the inner cylinder portion 30c to which the auxiliary substance is transferred. That is, the inner cylinder portion 30c is moved to a position where the tip portion of the inner cylinder portion 30c protrudes from the opening 11 of the needle tip portion 10, and the transfer control unit 41 moves the auxiliary substance from the side opposite to the tip portion of the inner cylinder portion 30c. The liquid is poured into the inner cylinder portion 30b. The auxiliary substance supplied to the inner cylinder portion 30c is a substance different from the auxiliary substance supplied to the inner cylinder portion 30b.

As a result, the auxiliary substance is released from the opening at the tip of the inner cylinder portion 30c through the inside of the inner cylinder portion 30c and is supplied around the cell group Cg. When a predetermined amount of the auxiliary substance is supplied in the vicinity of the cell group Cg, the supply of the auxiliary substance to the inner cylinder portion 30c is stopped, and the inner cylinder portion 30b is moved and pulled into the inside of the accommodating portion 15.

After that, the needle tip portion 10 is pulled out from the transplantation site. The needle tip portion 10 is pulled out from the transplantation site in a state where the inner cylinder portion 30c is not accommodated inside the accommodating portion 15 and the tip portion of the inner cylinder portion 30c protrudes from the opening 11 of the needle tip portion 10. May be good.

As described above, the transplantation of the cell group Cg into the target region and the supply of the auxiliary substance are completed. According to the present embodiment, since the cell transplantation device 100 includes an inner cylinder portion 30 for transferring the cell group Cg and an inner cylinder portion 30 for transferring the auxiliary substance, it is added to the cell group Cg. Therefore, the auxiliary substance can be taken into the cell transplantation device 100. Then, in a state where the needle tip portion 10 is stuck in the target region for transplantation, each inner cylinder portion 30 protrudes in order from the opening 11 of one needle tip portion 10 and releases the transfer target into the living body. Auxiliary substances can be placed near the region where the cell group Cg is placed. Therefore, the cell group Cg, the auxiliary substance, and the in vivo can be easily delivered.
In particular, the cell transplantation device 100 is preferably used when the auxiliary substance is a substance that is desired to be delivered into the living body at the timing of arranging the cell group Cg in the living body.

When the auxiliary substance is a substance that assists the expression of the function of the cell group Cg, the function of the cell group Cg is likely to be expressed by delivering the cell group Cg and the auxiliary substance into the living body using the cell transplantation device 100. Become. For example, when the cell group Cg is a cell group that contributes to hair growth or hair growth, such as a hair follicle primordium, hair formation preferably proceeds. Therefore, the cell transplantation device 100 is suitably used, for example, for transplantation into the cell group Cg to a place where hair is surely to be generated.

When the auxiliary substance is a substance that assists the entry or withdrawal of the needle-shaped portion 20 into the living body, the cell group Cg and the auxiliary substance are delivered into the living body by using the cell transplantation device 100 to form a needle-shaped part. The piercing of the part 20 into the living body is smoothly proceeded.

In the above description of the transplantation method, the cell group Cg was first transplanted into the living body, and then the auxiliary substance was supplied, but the order of delivery of the cell group Cg and the auxiliary substance is not particularly limited. The cell group Cg may be transplanted after the auxiliary substance is supplied, or the cell group Cg may be transplanted between the supply of the plurality of auxiliary substances.

Further, in the above description of the transplantation method, the auxiliary substance is supplied into the inner cylinder portion 30 after the needle tip portion 10 is pierced into the living body, but the auxiliary substance is applied to the inner cylinder portion before the needle tip portion 10 is pierced into the living body. The portion 30 may be filled. In this case, when supplying the auxiliary substance into the living body, the tip of the inner cylinder portion 30 filled with the auxiliary substance is projected from the opening 11 of the needle tip portion 10 pierced by the living body, and then the inner cylinder portion. The inside of 30 is pressurized. As a result, the auxiliary substance in the inner cylinder portion 30 is released into the living body from the tip portion of the inner cylinder portion 30.

Further, when the auxiliary substance is a liquid, as described above, the auxiliary substance may be taken into the inside of the inner cylinder portion 30 through the opening of the tip portion of the inner cylinder portion 30. For example, when an auxiliary substance is taken in from the tip of the inner cylinder 30b, the tip of the inner cylinder 30b is the needle tip 10 before or after the cell group Cg is taken into the inner cylinder 30a from the tray 50. The tip of the inner cylinder portion 30b is inserted into the container containing the auxiliary substance, and the inside of the inner cylinder portion 30b is sucked. As a result, the auxiliary substance is taken into the inner cylinder portion 30b from the tip portion of the inner cylinder portion 30b. When supplying the auxiliary substance into the living body, the inside of the inner cylinder portion 30b is pressurized with the tip of the inner cylinder portion 30b protruding from the opening 11 of the needle tip portion 10 pierced by the living body. As a result, the auxiliary substance in the inner cylinder portion 30b is released into the living body from the tip portion of the inner cylinder portion 30b.

When the auxiliary substance is other than a liquid, the auxiliary substance is taken up in the same manner as the uptake of the cell group Cg. For example, when the inner cylinder portion 30b holds an auxiliary substance other than a liquid, the tip portion of the inner cylinder portion 30b is the opening of the needle tip portion 10 before or after the cell group Cg is taken into the inner cylinder portion 30a from the tray 50. With the state protruding from 11, the tip portion of the inner cylinder portion 30b is brought close to the auxiliary substance, and the inside of the inner cylinder portion 30b is sucked. As a result, the auxiliary substance is taken into the inside of the inner cylinder portion 30b from the opening of the tip portion of the inner cylinder portion 30b. When supplying the auxiliary substance into the living body, the inside of the inner cylinder portion 30 is pressurized with the tip of the inner cylinder portion 30b protruding from the opening 11 of the needle tip portion 10 pierced by the living body. As a result, the auxiliary substance in the inner cylinder portion 30 is released from the tip portion of the inner cylinder portion 30 and placed in the living body.

Further, when the auxiliary substance is other than a liquid, as described above, the auxiliary substance may be held outside the tip portion of the inner cylinder portion 30 by suction inside the inner cylinder portion 30. However, in order to prevent the auxiliary substances from coming into contact with each other and the auxiliary substances from coming into contact with the cell group Cg in the needle-shaped portion 20 when the cell transplantation device 100 is moved to the transplantation site, the auxiliary substance is other than a liquid. In this case, the auxiliary substance is preferably taken up inside the inner cylinder portion 30, and the cell group Cg is also preferably taken up inside the inner cylinder portion 30.

[Modification example]
The tip of the needle-shaped portion 20 has an inner diameter that allows two or more inner cylinders 30 to pass through at the same time, and the opening 11 allows the tips of two or more inner cylinders 30 to protrude at the same time. May have a large size.

For example, in the cell transplantation device 110 shown in FIG. 8, the needle-shaped portion 20 extends with a constant inner diameter, and has a shape corresponding to a shape in which the needle tip portion 10 and the accommodating portion 15 are continuous with the same inner diameter. doing. The needle-shaped portion 20 has an inner diameter large enough to accommodate all the inner cylinder portions 30 together.

Then, the drive unit 40 simultaneously moves all the inner cylinder portions 30 along the extending direction of the needle-shaped portion 20. That is, the drive unit 40 is between a state in which the tips of all the inner cylinders 30 are located inside the needle-shaped portion 20 and a state in which the tips of all the inner cylinders 30 protrude from the opening 11. , These inner cylinder portions 30 are moved relative to the needle-shaped portion 20. FIG. 9 shows a state in which the tip portions of all the inner cylinder portions 30a protrude from the opening 11. FIG. 9 shows a form in which the positions of the tips of all the inner cylinders 30a are aligned in the extending direction of the needle-shaped portion 20, but the positions of the tips of the plurality of inner cylinders 30 are aligned. It may be moved at the same time without it. For example, the tip of the inner cylinder portion 30 for transferring the cell group Cg may protrude downward from the other inner cylinder portion 30.

When a cell group is transplanted using the cell transplant device 110, after the cell group Cg is held in the inner cylinder portion 30 for transfer of the cell group Cg, the tips of all the inner cylinder portions 30 are needles. The tip of the needle-shaped portion 20 is stabbed into the transplantation site while being located inside the shaped portion 20. Then, all the inner cylinders 30 are moved at the same time, and the tips of all the inner cylinders 30 are in a state of protruding from the opening 11. The uptake of the auxiliary substance into the inner cylinder portion 30 is performed before or after the needle-shaped portion 20 is stabbed at the transplantation site, as in the above embodiment. Then, the cell group Cg and the auxiliary substance are released from the tip of the inner cylinder portion 30 corresponding to each of the cell group Cg and the auxiliary substance, so that the cell group Cg and the auxiliary substance are delivered into the living body.

The release of the cell group Cg and the release of the auxiliary substance may be performed in a predetermined order. Alternatively, the release of the cell group Cg and the release of one or more auxiliary substances may be performed at the same time, or the release of a plurality of auxiliary substances may be performed at the same time.

As described above, if the plurality of inner cylinders 30 are moved at the same time, the configuration for moving the inner cylinders 30 and the movement of the plurality of inner cylinders 30 can be easily controlled.
Even when the tip of the needle-shaped portion 20 has an inner diameter that allows the plurality of inner cylinder portions 30 to pass through at the same time, the plurality of inner cylinder portions 30 may have the same inner diameter as in the above embodiment. , The inner cylinder portion 30 may be moved for each inner cylinder portion 30, and the inner cylinder portion 30 may be taken in and out one by one from the opening 11. Further, a plurality of inner cylinders 30 which are a part of all the inner cylinders 30 may be taken in and out from the opening 11 at the same time. For example, two of the three inner cylinders 30 may be taken in and out of the opening 11 at the same time.

Further, it may be possible to move the plurality of inner cylinder portions 30 at the same time and to move the plurality of inner cylinder portions 30 one by one. In this case, for example, in one of the uptake of the cell group Cg and the auxiliary substance and the release of the cell group Cg and the auxiliary substance, the plurality of inner cylinders 30 are simultaneously moved, and in the other, the plurality of inner cylinders 30 are 1. It may be moved one by one.

Further, as in the cell transplantation device 120 shown in FIG. 10, a plurality of needle-shaped portions 20 may be provided. The cell transplantation device 120 includes a plurality of needle-shaped portions 20, and a plurality of inner cylinder portions 30 for each needle-shaped portion 20. In each needle-shaped portion 20, the plurality of inner cylinder portions 30 include an inner cylinder portion 30 for transferring a cell group and an inner cylinder portion 30 for transferring an auxiliary substance. FIG. 10 shows a form in which the opening 11 at the tip of the needle-shaped portion 20 has a size for passing a plurality of inner cylinder portions 30 one by one, but as described with reference to FIG. 8 above. The opening 11 may have a size that allows a plurality of inner cylinders 30 to pass through at the same time. In each needle-shaped portion 20, the plurality of inner cylinder portions 30 are moved one by one or at the same time in the same manner as described above, and are taken in and out from the opening 11 at the tip of the needle-shaped portion 20.

The arrangement of the plurality of needle-shaped portions 20 is not particularly limited, and the plurality of needle-shaped portions 20 may be arranged regularly or irregularly. When the cell transplantation device 120 includes a plurality of needle-shaped portions 20, a plurality of cell group Cg can be collectively accommodated in the cell transplantation device 120, or a plurality of cell group Cg can be collectively arranged in a target region for transplantation. Is possible. Therefore, the efficiency of transplantation of the cell group Cg is enhanced.

As described above, according to the above-described embodiment and modification, the effects listed below can be obtained.
(1) Since the cell transplantation device 100 includes an inner cylinder portion 30 for transferring the cell group Cg and an inner cylinder portion 30 for transferring an auxiliary substance, the inside of one needle-shaped portion 20 The cell group Cg and auxiliary substances can be taken up and transferred into the living body. Then, since the cell group Cg and the auxiliary substance can be released from one needle-shaped portion 20, the auxiliary substance can be supplied to the vicinity of the region where the cell group Cg is arranged in the living body. Therefore, the cell group Cg, the auxiliary substance, and the in vivo can be easily delivered.

(2) The inner cylinder portion 30 is in the first state in which the tip portion of the inner cylinder portion 30 is located inside the needle-shaped portion 20, and the tip portion of the inner cylinder portion 30 is the opening 11 of the tip portion of the needle-shaped portion 20. It is movable relative to the needle-shaped portion 20 with respect to the second state protruding from. Therefore, the needle-shaped portion 20 can be pierced into the living body in the first state, and the cell group Cg and the auxiliary substance can be taken in and released in the second state. Therefore, the delivery of the cell group Cg and the auxiliary substance into the living body is smoothly promoted.

(3) If the plurality of inner cylinder portions 30 are moved between the first state and the second state for each inner cylinder portion 30, the plurality of inner cylinder portions 30 are needle-shaped one by one. Since it can be taken in and out from the opening 11 of the portion 20, the cell group Cg and the auxiliary substance can be taken in and released in a state where there is a margin in the space around the inner cylinder portion 30. Therefore, these operations can proceed smoothly.

(4) If two or more inner cylinder portions 30 are simultaneously moved between the first state and the second state, the case where a plurality of inner cylinder portions 30 are moved one by one is compared with the case where the plurality of inner cylinder portions 30 are moved one by one. Therefore, the movement of the inner cylinder portion 30 can be easily controlled.

(5) The inner cylinder portion 30 for transferring the cell group Cg is connected to a mechanism for sucking the inside of the inner cylinder portion 30, and the cell group Cg is transferred from the tip end portion of the inner cylinder portion 30 into the inner cylinder portion 30 by the suction. To capture. According to this, when the cell group Cg is an aggregate of cells, the cell group Cg can be accurately taken into the inner cylinder portion 30, and a desired number of cell group Cg can be taken into the inner cylinder portion 30. It is also easy to take in.

(6) The inner cylinder portion 30 for transferring the auxiliary substance takes in the auxiliary substance which is a liquid into the inner cylinder portion 30 from the side opposite to the tip portion of the inner cylinder portion 30. According to this, it is possible to efficiently take in the auxiliary substance into the inner cylinder portion 30 by taking advantage of the characteristics of the liquid. In addition, by changing whether the transfer target is taken in from the distal end side or the proximal end side of the inner cylinder portion 30 between the cell group Cg and the auxiliary substance, accurate uptake can be performed according to the characteristics of the transfer target. ..

(7) The cell transplantation device 120 includes a plurality of needle-shaped portions 20, and for each needle-shaped portion 20, an inner cylinder portion 30 for transferring the cell group Cg and an inner cylinder portion 30 for transferring an auxiliary substance are provided. It is provided with a plurality of inner cylinder portions 30 including and. According to this, a plurality of cell group Cg and auxiliary substances can be collectively taken into the cell transplantation device 120, and a plurality of cell group Cg and auxiliary substances can be collectively arranged in a living body, so that the transplantation can be performed. Efficiency is increased.

[Other variants]
The above-described embodiment and modification can be modified and implemented as follows.
-In at least one of the uptake of the cell group Cg and the auxiliary substance and the release of the cell group Cg and the auxiliary substance, the plurality of inner cylinder portions 30 have the tips of the plurality of inner cylinder portions 30 inside the needle-shaped portion 20. It does not have to be moved from its position. For example, as shown in FIG. 8 above, in a form in which the opening 11 has a size for passing a plurality of inner cylinders 30 at the same time, the tips of the plurality of inner cylinders 30 are inside the needle-shaped portion 20. The uptake and release of the cell group Cg and the auxiliary substance may be carried out in a state of being located near the opening 11. If the plurality of inner cylinders 30 are not moved by both the uptake and release of the cell group Cg and the auxiliary substance, the cell transplantation device may not include the drive unit 40.

-The inner cylinder portion 30 can be used as both a first inner cylinder portion for transferring the cell group Cg and a second inner cylinder portion for transferring an auxiliary substance, and the first inner cylinder portion can be used. It may be decided at the time of use whether it is used as a second inner cylinder portion or as a second inner cylinder portion.

-The inner cylinder portion 30 can be attached to and detached from the inside of the needle-shaped portion 20, and the inner cylinder portion 30 attached to the cell transplantation device can be increased / decreased or replaced according to the type and number of auxiliary substances desired to be supplied. It may be done.

-The substances to be transferred in the second inner cylinder are not limited to substances that assist the expression of the function of the cell group and substances that assist the entry and withdrawal of the needle-shaped portion 20 into the living body, and together with the cell group. Any substance that exerts a predetermined function when supplied into a living body may be used.

-The cell group to be transplanted does not have to be a cell group that contributes to hair growth or hair growth, and may be a cell group that exerts a desired effect by being arranged in a living body. For example, the cell group to be transplanted may be a cell group that exerts an effect for cosmetic purposes such as elimination of wrinkles on the skin and improvement of a moisturizing state.

[Example]
The above-mentioned cell transplantation device will be described with reference to specific examples.
As an example, a cell transplantation device corresponding to FIG. 8 was manufactured. The cell transplantation apparatus of the embodiment includes two inner cylinder portions, one first inner cylinder portion and one second inner cylinder portion. As the needle-shaped part, a 17G injection needle was used. The inner diameter of the needle-shaped portion is 1.10 mm, and the outer diameter of the needle-shaped portion is 1.46 mm. As the first inner cylinder portion and the second inner cylinder portion, precision pipes having an inner diameter of 0.17 mm and an outer diameter of 0.36 mm were used. Two inner cylinders were arranged inside the needle-shaped portion, and a syringe was connected to the base end of each inner cylinder via a tube.

As a model of the cell group, plastic beads having an average particle size of 210 μm were prepared, and pure water was prepared as a model of an auxiliary substance. By sucking the inside of the inner cylinder portion using a syringe, one plastic bead was taken into the first inner cylinder portion from the tip portion thereof, and pure water was taken into the second inner cylinder portion from the tip portion thereof.

The test of administering the plastic beads and pure water taken into the cell transplantation device to a silicone test piece, which is a substitute for a living body, was carried out five times. After each test, it was confirmed whether the plastic beads and pure water were arranged inside the test piece. In all five tests, the plastic beads and pure water remained inside the needle-shaped part. It was confirmed that it was placed inside the test piece. Therefore, it was confirmed that the cell group and the auxiliary substance can be delivered to the subject using the cell transplantation device of the example.

Cg ... Cell group, Pl ... Protective solution, Sl ... Auxiliary substance, 10 ... Needle tip, 11 ... Opening, 15 ... Containment part, 20 ... Needle-shaped part, 30 ... Inner cylinder part, 40 ... Drive part, 41 ... Transfer control unit, 100, 110, 120 ... Cell transplantation device.

Claims (7)

A cell transplantation device for arranging a group of cells in a target area in a living body.
A tubular needle that extends in one direction,
A plurality of inner cylinder portions located inside the needle-shaped portion are provided.
A cell transplantation apparatus including a first inner cylinder portion for transferring the cell group and a second inner cylinder portion for transferring a substance other than the cell group in the plurality of inner cylinder portions. The inner cylinder portion has a first state in which the tip portion of the inner cylinder portion is located inside the needle-shaped portion and a first state in which the tip portion of the inner cylinder portion protrudes from the opening of the tip portion of the needle-shaped portion. The cell transplantation apparatus according to claim 1, which is configured to be movable relative to the needle-shaped portion between the two states. The cell transplantation apparatus according to claim 2, wherein the plurality of inner cylinder portions are configured to be movable between the first state and the second state for each inner cylinder portion. The cell transplantation apparatus according to claim 2, wherein two or more inner cylinder portions are configured to be movable between the first state and the second state at the same time. The cell group is an aggregate of cells.
The first inner cylinder portion is connected to a mechanism for sucking the inside of the first inner cylinder portion, and the cell group is taken into the first inner cylinder portion from the tip end portion of the first inner cylinder portion by the suction. 4. The cell transplantation apparatus according to any one of 4. The at least one second inner cylinder portion included in the plurality of inner cylinder portions is the second inner cylinder portion for transferring a liquid which is a substance other than the cell group, and is the second inner cylinder portion of the second inner cylinder portion. The cell transplantation apparatus according to any one of claims 1 to 5, wherein the substance is taken into the second inner cylinder portion from the side opposite to the tip portion. With a plurality of the needle-shaped portions,
The cell transplantation apparatus according to any one of claims 1 to 6, wherein each needle-shaped portion includes a plurality of the inner cylinder portions including the first inner cylinder portion and the second inner cylinder portion.

Images