JP7230643B2 - Living body transfer device, member for living body transfer device, living body transfer unit, and living body transfer kit - Google Patents

Description

TECHNICAL FIELD The present invention relates to a biological transfer device, a biological transfer device member, a biological transfer unit, and a biological transfer kit, which are used for transferring an object into a living body.

Techniques have been developed for intradermally or subcutaneously transplanting implants obtained by culturing cells collected from living organisms. For example, attempts have been made to regenerate hair by purifying a group of cells that contributes to the formation of hair follicles, which are organs that produce hair, and transplanting this group of cells into the skin.

Hair follicles are formed by interactions between epithelial cells and mesenchymal cells. For good hair regeneration, it is desirable that the transplanted cell population should give rise to hair follicles with normal tissue architecture and the ability to form periodic hairs. Therefore, various researches and developments have been conducted on methods for producing cell groups capable of forming such hair follicles (see, for example, Patent Documents 1 to 3).

WO2017/073625 WO2012/108069 Japanese Unexamined Patent Application Publication No. 2008-29331

By the way, for the smooth transplantation of the transplant, it is desirable that the transplant placed in a container such as a culture vessel can be smoothly moved into the living body. For example, in the transplantation method, in which the skin is incised with a scalpel and the cells in the culture vessel are picked up one by one with tweezers or the like and transferred into the skin, the instruments used must be replaced and the movement of the cells must be repeated frequently. Therefore, it is difficult to say that transplantation proceeds smoothly.
In addition, such a problem is common not only when transferring solid substances such as drugs, but also when placing them in a living body.

An object of the present invention is to provide a biological transfer device, a biological transfer device member, a biological transfer unit, and a biological transfer kit that enable smooth transfer of an object into a living body.

A biological transfer device for solving the above problems is a biological transfer device for arranging an object in a living body, comprising a cylindrical needle-like portion extending along one direction, the needle-like portion The needle-shaped portion that takes in the object from an opening located at the tip of the needle-shaped portion, and a tubular portion that is located outside or inside the needle-shaped portion, the tubular portion being positioned further than the tip of the needle-shaped portion. the tubular portion configured to be movable along the extending direction of the needle-like portion from a state in which the distal end portion of the shaped portion protrudes; The length of the opening located at the tip of the needle is smaller than the length of the opening located at the tip of the needle.

A member for a living body transfer device that solves the above problems includes a cylindrical needle-like portion that extends along one direction, and takes in an object from an opening positioned at the tip of the needle-like portion, A member attached to a device for placing the object in the body, comprising a cylindrical portion that is fitted to the outside of the needle-like portion and configured to be slidable along the outer peripheral surface of the needle-like portion, In the extending direction of the needle-like portion, the length of the opening positioned at the tip of the tubular portion is smaller than the length of the opening positioned at the tip of the needle-like portion.

A living body transfer unit that solves the above problems includes a tray having one or more planned placement areas where an object is to be placed, and a living body transfer device for transferring the object from the tray into the living body. and, wherein the biological transfer device is a cylindrical needle-like portion extending along one direction, and the opening located at the distal end of the needle-like portion extends from the The needle-shaped portion that takes in the object located in the arrangement planned area, and the tubular portion that is located outside or inside the needle-shaped portion, and the tubular portion is positioned closer to the tip portion of the needle-shaped portion. and the cylindrical portion configured to be movable along the direction in which the needle-like portion extends from a state in which the tip portion of the needle-like portion protrudes, and one needle-like portion for one of the arrangement planned regions. is assigned, and the length of the opening located at the distal end of the tubular portion is smaller than the length of the opening located at the distal end of the needle-shaped portion in the extending direction of the needle-shaped portion.

A living body transfer kit for solving the above problems includes a tray having a plurality of planned arrangement areas where objects are planned to be arranged; a member attached to a device that takes in the object located in the planned arrangement area from an opening located at the tip of the shaped portion and moves the object from the tray into the living body. wherein the member includes a plurality of cylindrical portions that are fitted to the outside of the needle-like portion and configured to be slidable along the outer peripheral surface of the needle-like portion; wherein the length of the opening located at the distal end of the tubular portion is smaller than the length of the opening located at the distal end of the needle-shaped portion, and one tubular portion is provided for each planned arrangement region. is assigned.

According to each of the above configurations, the transport device for a living body takes the object into the interior of the needle-like portion from the opening at the distal end of the needle-like portion, pierces the living body with the needle-like portion, and then moves the object through the needle-like portion. It is discharged from the opening. By using such a device, it is possible to continuously perform the process from taking out the object from the tray to placing it in the living body with one device, so that the object can be transferred smoothly.

By setting the tip portion of the tubular portion to protrude beyond the tip portion of the needle-shaped portion, the tubular portion into which the object is captured can be targeted as compared with a form in which the tubular portion is not provided. Objects can be taken in by approaching them. Therefore, the object can easily enter the tubular portion, and as a result, the object can be smoothly taken into the needle-like portion. Therefore, the object can be transferred more smoothly.

The said structure WHEREIN: The plane orthogonal to the direction where the said needle-shaped part is extended may be sufficient as the end surface with which the front-end|tip part of the said cylindrical part is provided.
According to the above configuration, when capturing the object, the cylindrical portion into which the object is captured can be brought closer to the object. Therefore, the object can easily enter the cylindrical portion.

The said structure WHEREIN: The end surface with which the front-end|tip part of the said cylindrical part is provided may have unevenness|corrugation with respect to the plane orthogonal to the extending direction of the said needle-shaped part.
According to the above configuration, when the object is taken in, even if the tip of the cylindrical portion is brought into contact with the tray holding the object, a gap is formed between the concave portion of the end face and the tray. , it is possible to continue the suction for the capture of the object. Therefore, it is possible to smoothly take in the target object.

In the above configuration, the end surface of the distal end portion of the needle-like portion includes an inclined portion that is inclined inward in the radial direction so as to approach the base end portion of the needle-like portion, and the inclined portion includes: A base end portion of the end surface in the direction in which the needle-like portion extends may be included.
According to the above configuration, it is possible to prevent the object from being caught on the end surface of the needle-like portion when the object is taken in.

In the above configuration, at least one of the inner peripheral surface of the needle-shaped portion and the inner peripheral surface of the tubular portion may be made of a material that suppresses adhesion of the target.
According to the above configuration, the object that has entered the tubular portion easily flows into the needle-shaped portion.

The said structure WHEREIN: The said cylindrical part is located in the outer side of the said needle-like part, and may be comprised along the outer peripheral surface of the said needle-like part so that a slide is possible.

According to the above configuration, the assembly and movement of the tubular portion with respect to the needle-shaped portion are simplified compared to arranging the tubular portion inside the needle-shaped portion. In particular, since the cylindrical portion can be easily moved to expose the distal end of the needle-like portion, the object can be quickly placed in the living body after the object is taken into the needle-like portion. be able to.

According to the present invention, the object can be smoothly transferred into the living body.

1 is a diagram showing the overall configuration of a cell transplantation device, which is an example of a biological transfer device, in one embodiment of a biological transfer device; FIG. The figure which shows the cross-sectional structure of the needle-shaped part and outer cylinder part with which the cell transplantation apparatus of one Embodiment is provided. The figure which shows an example of the cross-sectional structure of the cell transplantation apparatus of one Embodiment. FIG. 2 is a diagram showing a cross-sectional structure of a cell transplantation device according to an embodiment, in which a plurality of needle-like portions are provided; FIG. 2 is a diagram showing the arrangement of a cell transplantation device and a tray holding a transplant in a transplantation method using the cell transplantation device of one embodiment. FIG. 10 is a diagram showing another example of the arrangement of the cell transplantation device and the tray holding the transplant in the transplantation method using the cell transplantation device of one embodiment. FIG. 10 is a diagram showing another example of the arrangement of the cell transplantation device and the tray holding the transplant in the transplantation method using the cell transplantation device of one embodiment. FIG. 4 shows a step of accommodating a transplant in a transplantation method using a cell transplantation device according to one embodiment; FIG. 4 shows a step of accommodating a transplant in a transplantation method using a cell transplantation device according to one embodiment; FIG. 4 is a diagram showing an example of movement of an outer cylinder in a transplantation method using a cell transplantation device according to one embodiment; FIG. 4 is a diagram showing an example of movement of an outer cylinder in a transplantation method using a cell transplantation device according to one embodiment; FIG. 4 shows a step of placing a transplant in a transplantation method using the cell transplantation device of one embodiment. FIG. 4 shows a step of placing a transplant in a transplantation method using the cell transplantation device of one embodiment. FIG. 4 is a diagram showing the arrangement of the device and the tray when a cell transplantation device having a plurality of needle-like portions is used in the transplantation method using the cell transplantation device of one embodiment. The figure which shows the cross-sectional structure of the needle-shaped part and outer cylinder part with which the cell transplantation apparatus of a modification is provided. The figure which shows the side structure of the needle-shaped part with which the cell transplantation apparatus of a modification is provided. The figure which shows the cross-sectional structure of the needle-shaped part and outer cylinder part with which the cell transplantation apparatus of a modification is provided. The figure which shows the cross-sectional structure of the needle-shaped part and outer cylinder part with which the cell transplantation apparatus of a modification is provided. The figure which shows the cross-sectional structure of the needle-shaped part and outer cylinder part with which the cell transplantation apparatus of a modification is provided with a tray.

One embodiment of a biological transfer device, a biological transfer device member, a biological transfer unit, and a biological transfer kit will be described with reference to FIGS. 1 to 14. FIG. The biological transfer device of this embodiment is embodied as a cell transplantation device used for cell transplantation.

[Transplant]
The cell transplantation device of this embodiment is used for transplanting a group of cells into a living body as a transplant. The target area for transplantation is at least one of intracutaneous and subcutaneous tissue, or tissue such as an organ. First, the cell group to be transplanted will be described.

A cell group to be transplanted includes a plurality of cells. A cell group may be an aggregation of a plurality of aggregated cells, or an aggregation of a plurality of cells bound by intercellular junctions. Alternatively, the cell population may consist of a plurality of dispersed cells. In addition, the cells that constitute the cell group may be undifferentiated cells or cells that have completed differentiation, and the cell group includes undifferentiated cells and differentiated cells. good too. Cell groups are, for example, cell clusters (spheroids), primordia, tissues, organs, organoids, mini-organs, and the like.

A group of cells has the ability to affect tissue formation in a living body by being placed in a region of interest. One example of such cell populations are cell aggregates containing cells with stemness. The cell group to be transplanted contributes to hair growth or restoration by, for example, being placed intracutaneously or subcutaneously. These cell groups have the ability to function as hair follicle organs, the ability to differentiate into hair follicle organs, the ability to induce or promote the formation of hair follicle organs, or the ability to induce or promote hair formation in hair follicles. . The cell group may also contain 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 contain vascular cells.

Specifically, one example of a cell group to be transplanted in the present embodiment is a hair follicle primordium, which is a primitive hair follicle organ. A hair follicle primordium contains mesenchymal cells and epithelial cells. In the hair follicle organ, dermal papilla cells, which are mesenchymal cells, induce the differentiation of hair follicle epithelial stem cells, and hair is formed by repeated division of hair matrix cells in the hair bulb formed by this. be. A hair follicle primordium is a group of cells that differentiate into such hair follicle organs.

For the hair follicle primordium, for example, mesenchymal cells derived from the mesenchymal tissue such as the dermal papilla and epithelial cells derived from the epithelial tissue located in the bulge region, hair bulb base, etc. are mixed under predetermined conditions. Formed by culturing. However, the method for producing the hair follicle primordia is not limited to the above example. In addition, the origin of the mesenchymal cells and epithelial cells used for the production of the hair follicle primordium is not limited, and these cells may be cells derived from the hair follicle organ. Cells derived from different organs may be used, or cells derived from pluripotent stem cells may be used.
In addition, the implant may contain a member that assists the transplantation of the cell group together with the cell group.

[Cell transplantation device]
As shown in FIG. 1, the cell transplantation device 100 includes a needle-like portion 10 extending along one direction, an outer cylinder portion 20 positioned outside the needle-like portion 10, and a support portion supporting the needle-like portion 10. 30. The outer tubular portion 20 is an example of a tubular portion. Furthermore, the cell transplantation device 100 includes a suction section 40 that suctions the inside of the needle-like section 10 . Note that the support portion 30 may also serve as the suction portion 40 .

First, detailed configurations of the needle-like portion 10 and the outer tube portion 20 will be described. As shown in FIG. 2, the needle-like portion 10 has a tubular shape and an opening 11 at its distal end. The distal end portion of the needle-like portion 10 has a shape obtained by cutting a cylinder obliquely with respect to the direction in which it extends, and is pointed. The outer shape of the needle-like portion 10 is not particularly limited, but for example, the needle-like portion 10 extends in a cylindrical shape, and the tip portion of the needle-like portion 10 has a shape obtained by cutting the cylinder obliquely with respect to the extending direction. An end surface 12 of the distal end portion of the needle-like portion 10, that is, an end surface 12 that defines the opening 11, is inclined with respect to the extension direction, which is the direction in which the needle-like portion 10 extends.

The outer cylinder part 20 has a tubular shape fitted on the outside of the needle-like part 10 . The outer tube portion 20 extends in the same direction as the needle-like portion 10, that is, along the extending direction. The distal end portion of the needle-like portion 10 is passed through the inside of the outer tube portion 20 , and the outer peripheral surface of the needle-like portion 10 is in contact with the inner peripheral surface of the outer tube portion 20 . As long as the inner peripheral surface of outer cylinder 20 has a shape along the outer peripheral surface of needle-like portion 10, the outer shape of needle-like portion 10 is not particularly limited. For example, when the needle-like portion 10 extends in a cylindrical shape, if the inner peripheral surface of the outer tube portion 20 is cylindrical, the outer peripheral surface of the outer tube portion 20 may be cylindrical or rectangular. may

The end surface 22 of the distal end portion of the outer cylinder portion 20, that is, the end surface 22 defining the opening 21 of the outer cylinder portion 20 at the distal end portion, is a plane orthogonal to the extending direction. In such a configuration, the length Lt of the opening 21 of the outer tube portion 20 in the extending direction is 0, and the length Lt is smaller than the length Ln of the opening 11 of the needle-like portion 10 in the extending direction.

The outer tube portion 20 is configured to be slidable along the needle-like portion 10 . Specifically, the state in which the opening 11 of the needle-like portion 10 is located inside the outer tube portion 20 is changed to the state where the opening 11 of the needle-like portion 10 is positioned inside the outer tube portion 20 by moving the outer tube portion 20 along the needle-like portion 10 . It is possible to switch to a state in which the opening 11 of the shaped portion 10 is exposed. In other words, the outer cylinder part 20 is configured to be movable along the needle-like part 10 from a state in which the tip part of the outer cylinder part 20 protrudes from the tip part of the needle-like part 10 .
In addition, the length of the outer cylinder part 20 in the extension direction may be any length that allows the opening 11 of the needle-like part 10 to be accommodated inside the outer cylinder part 20 .

Materials for the needle-like portion 10 and the outer tube portion 20 are not particularly limited. Each of the needle-like portion 10 and the outer tube portion 20 is made of metal or resin, for example. Examples of the resin material forming the outer tube portion 20 include fluororesin and silicone. If the outer cylinder part 20 is transparent, it is easy to confirm that the implant has been taken into the outer cylinder part 20 .

The outer tube portion 20 may be elastically deformable and attached to the needle-like portion 10 using elasticity. Alternatively, the outer tube part 20 may be attached to the needle-like part 10 by using a member for fixing the outer tube part 20 to the needle-like part 10 . In addition, the needle-like portion 10 and the outer tube portion 20 may have structures such as grooves and projections for locking the outer tube portion 20 at a predetermined position with respect to the needle-like portion 10 .

At least one of the inner peripheral surface of the needle-like portion 10 and the inner peripheral surface of the outer tube portion 20 is preferably made of a material that suppresses adhesion of the implant. For example, the material constituting the tubular structure of the needle-shaped portion 10 and the outer tubular portion 20 may have a property of suppressing adhesion of the implant, or the inner peripheral surface of the tubular structure may be coated. A surface layer may be formed and the surface layer may have properties that reduce adhesion of the implant. Materials for forming the surface layer include, for example, silicone and polyethylene glycol.

The internal space of the needle-like portion 10 may have a size suitable for accommodating the implant. For example, if the implant is a cell group that contributes to hair growth or hair growth and is an aggregate of cells such as a cell cluster or primordium, the internal space of the needle-like portion 10 accommodates one implant. It preferably has a size suitable for that purpose. Specifically, the inner diameter of the needlelike portion 10 is preferably larger than the diameter of the expected implant. For example, the diameter of the sphere when the cell cluster, which is an aggregate of cells, is approximated to a sphere, that is, the diameter of the smallest sphere that circumscribes the cell cluster is about 0.1 mm to 1.0 mm. As the needle-like portion 10, for example, a 25G injection needle can be used. In this case, the inner diameter of the needle-like portion 10 is 0.4 mm, the outer diameter of the needle-like portion 10 is 0.5 mm, and the length from the tip to the proximal end of the end face 12 of the needle-like portion 10 in the extending direction is , 2.8 mm.

The outer diameter of the needle-like portion 10 is preferably as small as possible within the range in which the strength of the needle-like portion 10 is ensured. The smaller the outer diameter of the needle-like portion 10, the smaller the thickness of the side wall of the needle-like portion 10. Therefore, when the implant is taken into the inside of the needle-like portion 10, the implant is less likely to be caught on the end of the side wall. . Specifically, the thickness of the side wall of needle-like portion 10 is preferably 50 μm or less.

The support portion 30 may be a member formed separately from the needle-like portion 10 or may be integrally formed with the needle-like portion 10 . If the support part 30 is a member formed separately from the needle-like part 10 , the support part 30 surrounds the outside of the portion extending from the distal end of the needle-like part 10 and supports the needle-like part 10 . For example, the needle-like portion 10 is assembled to the support portion 30 by passing the needle-like portion 10 through a hole of the support portion 30 . When the support portion 30 is integrally formed with the needle-like portion 10 , the needle-like portion 10 protrudes from the surface of the support portion 30 . The outer shape of the support portion 30 is not particularly limited.

The suction part 40 has a mechanism for sucking the inside of the needle-like part 10 . The suction part 40 may further have a function of pressurizing the inside of the needle-like part 10 with air pressure. FIG. 3 shows an example of a cell transplantation device 100 provided with a support section 30 that also serves as a suction section 40 having suction and pressurization functions inside the needle-shaped section 10 .

The support portion 30 shown in FIG. 3 has a syringe barrel-like configuration, and includes a barrel 31 connected to the proximal end portion of the needle portion 10 and a pusher 32 positioned inside the barrel 31. there is The tubular body 31 has a tubular shape with an inner diameter larger than that of the needle-like portion 10 . By pulling the pusher 32 in the cylindrical body 31, the inside of the needle-like portion 10 is sucked, and by pushing the pusher 32, the inside of the needle-like portion 10 is pressurized.
In addition, the suction part 40 is not limited to the above configuration, and may be provided with, for example, a pump mechanism or the like connected to the needle-shaped part 10, and suction and pressurization may be performed by driving such a mechanism.

The number of needle-like portions 10 provided in the cell transplantation device 100 is not particularly limited, and the cell transplantation device 100 may include a single needle-like portion 10 as shown in FIGS. may be provided with a plurality of needle-like portions 10 as shown. When the cell transplantation device 100 includes a plurality of needle-like parts 10, the arrangement of the needle-like parts 10 is not particularly limited, and the needle-like parts 10 may be arranged regularly or irregularly. You can stay. Moreover, when the cell transplantation device 100 includes a plurality of needle-like portions 10, it is preferable that one supporting portion 30 supports all the needle-like portions 10 collectively. That is, it is preferable that the cell transplantation device 100 in which the plurality of needle-like portions 10 are integrated is configured by supporting the plurality of needle-like portions 10 by one support portion 30 . In addition, the suction to the needle-like portion 10 may be performed independently for each needle-like portion 10, or may be performed to a plurality of needle-like portions 10 collectively.

When the cell transplantation device 100 has a plurality of needle-like portions 10 , the outer tube portion 20 is arranged for each of the plurality of needle-like portions 10 . The outer cylinder part 20 may be an independent cylinder for each needle-like part 10 , or the side walls of the outer cylinder part 20 adjacent to each other may be connected to form one member. When the side walls of the outer cylindrical portions 20 adjacent to each other are connected to each other, the side walls may be connected to each other at least partly in the extending direction. FIG. 4 illustrates a form in which a plurality of outer tube portions 20 are connected to form one member. In FIG. 4 , the side walls of the outer cylindrical portions 20 adjacent to each other are connected to each other throughout the extension direction.

When the cell transplantation device 100 includes a single needle-like portion 10, one outer cylindrical portion 20 constitutes a member for a biological transfer device, and when the cell transplantation device 100 includes a plurality of needle-like portions 10, A set of outer cylinders 20 attached to the needle-like part 10 constitutes a member for a biological transfer device. For example, as shown in FIG. 4, when a plurality of outer cylinders 20 are connected to form one member, this member 25 is the member for the biological transfer device.

[Transplantation method]
A method of transplanting a transplant using the cell transplantation device 100 will be described.
As shown in FIG. 5, before transplantation, the transplant Cg is held in a tray 50 such as a culture container together with a protective liquid Pl. For example, as shown in FIG. 5, the implant Cg and the protective liquid Pl are placed in the recess 51 of the tray 50, and the implant Cg is positioned near the bottom of the recess 51. As shown in FIG.

The manner in which the graft Cg and the protective solution Pl are held in the tray 50 is not limited to the form in which the graft Cg and the protective solution Pl are held in the concave portion 51 . For example, as shown in FIG. 6, the implant Cg may be positioned near the bottom of the recess 51, and the entire area of the tray 50 including the recess 51 and its upper portion may be filled with the protective liquid Pl. Alternatively, as shown in FIG. 7, the implant Cg and protective liquid Pl may be placed on the flat surface of the tray 50 . If the fluidity of the protective liquid Pl is low, it is possible to separate the transplants Cg together with the protective liquid Pl and arrange them on a plane.

In short, the tray 50 should have a planned placement area where the implant Cg is to be placed, and hold the implant Cg in the planned placement area. The planned arrangement area is, for example, the concave portion 51 or a predetermined area on a plane. When the tray 50 is a culture vessel and cells are cultured in the tray 50 to form the implant Cg, the tray 50 having the concave portion 51 facilitates cell culture. In addition, it is preferable that the tray 50 has a material to which cells are unlikely to adhere.

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, vaseline, or lotion, or a mixture of these liquids. The protective liquid Pl may contain additional components such as nutrients. In addition, when the tray 50 is a culture vessel and the transplant 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 implant Cg and the protective liquid Pl may be a low-viscosity fluid or a high-viscosity fluid. Moreover, the liquid body may have a structure in which the implant Cg and the protective liquid Pl are held in a matrix formed of a polymeric material or the like. At this time, examples of the polymer material forming the matrix include collagen and hyaluronic acid.

When the graft Cg is taken into the needle-like portion 10 , the cell transplantation device 100 is placed in a state where the opening 11 at the distal end of the needle-like portion 10 is positioned inside the outer cylinder portion 20 . That is, the distal end portion of the outer tube portion 20 is positioned at the distal end portion of the cell transplantation device 100 . Then, as shown in FIG. 8, the distal end of the outer cylinder 20 is brought close to the implant Cg in the protective liquid Pl, and the inside of the needle-like portion 10 is sucked by the operation of the suction section 40 . As a result, the inside of the outer cylinder part 20 is also sucked, and as shown in FIG. be Further, the implant Cg enters the interior of the needle-like portion 10 through the opening 11 of the needle-like portion 10 according to the flow of the protective liquid Pl caused by suction.

In order to take the implant Cg into the needle-like portion 10, the portion of the needle-like portion 10 where the side wall is cylindrical, that is, the proximal end side of the needle-like portion 10 from the proximal end portion of the opening 11, It is necessary to pull in the implant Cg.

In tray 50, implant Cg is submerged in protective liquid Pl. Therefore, when the outer cylinder part 20 is not provided, even if the tip part of the needle-like part 10 is brought close to the implant Cg, the distance corresponding to the length Ln of the opening 11 in the extending direction is the distance between the implant Cg and the implant Cg. It separates from the portion where the side wall is cylindrical. As a result, even if suction is performed, the implant Cg is less likely to enter the inside of the needlelike portion 10 . This problem becomes more pronounced as the length Ln of the opening 11 increases. It becomes difficult to take in the substance Cg.

If the tray 50 is vibrated to float the graft Cg, it becomes easier to take in the graft Cg. Incorporation of a large amount of the protective liquid Pl into the needle-like portion 10 at this time also causes a deterioration in the efficiency of transplantation.

On the other hand, in the cell transplantation device 100 of the present embodiment, when the graft Cg is taken into the needle-like portion 10, the distal end portion of the outer cylinder portion 20 protrudes from the distal end portion of the needle-like portion 10. . In the outer cylinder part 20, the side wall is cylindrical up to the end surface 22 of the tip part, and the implant Cg can be taken in by pulling the implant Cg into this cylindrical part. Therefore, compared to the case where the outer cylinder part 20 is not provided, the position where the implant Cg needs to be pulled can be brought closer to the implant Cg, so that the implant Cg can be taken in easily.

When the implant Cg is taken into the needle-like portion 10 , the outer tube portion 20 is moved to expose the opening 11 of the needle-like portion 10 from the outer tube portion 20 . As shown in FIG. 10, the opening 11 of the needle portion 10 may be exposed by moving the outer cylinder portion 20 toward the proximal end of the needle portion 10, or as shown in FIG. The opening 11 of the needle-like portion 10 may be exposed by moving the needle 20 to the distal end side of the needle-like portion 10 and removing it from the needle-like portion 10 . A portion of the needle-like portion 10 exposed from the outer tube portion 20 includes at least a portion that enters the living body when the implant Cg is placed in the target region for implantation. In addition, the movement of the outer cylinder part 20 may be performed manually, or may be electrically performed using a motor or the like.

In this embodiment, the distal end of the needle-like portion 10 is exposed by sliding the outer tube portion 20 relative to the needle-like portion 10, so that the step of exposing the distal end of the needle-like portion 10 can be easily performed. Therefore, after the implant Cg is taken into the needle-like portion 10, it can be quickly placed in the target region for transplantation, and deterioration of the implant Cg can be suppressed.

After exposing the tip of the needle 10, the cell transplantation device 100 is carried to the transplantation site such as the skin Sk of the living body, and as shown in FIG. 12, the needle 10 is stuck in the transplantation site. At this time, the tip portion of the needle-like portion 10 is exposed and has a shape that allows the tip portion of the needle-like portion 10 to easily stick into the transplantation site, so that the cell transplantation device 100 can smoothly enter the transplantation site. As a result, the distal end portion of the needle-like portion 10 enters the implantation site, and the opening 11 is arranged in the implantation target region. When trying to transplant a cell group that contributes to hair growth or hair growth, the target area is at least one of intradermal and subcutaneous.

As shown in FIG. 13, for example, by pressurizing the inside of the needle-like portion 10, the implant Cg housed inside the needle-like portion 10 comes out from the opening 11 together with the protective liquid Pl. This places the implant Cg in the target area. The needle 10 is then withdrawn from the implantation site.

Transplantation of the implant Cg to the target region is completed as described above. According to the above-described transplantation method using the cell transplantation device 100, it is possible to continuously perform the steps from removing the transplant Cg from the tray 50 to arranging it in the target region for transplantation by one device, so that cells can be smoothly transplanted. is possible.

FIG. 14 shows one step of a transplantation method using a cell transplantation device 100 having multiple needle-like portions 10 . FIG. 14 illustrates a configuration in which a plurality of outer cylinders 20 are connected at their proximal end portions in the extending direction to form a member 25 that is a member for a living body transfer device.

When the cell transplantation device 100 having a plurality of needle-like portions 10 is used, the positions of the cell transplantation device 100 and the tray 50 are adjusted so that each needle-like portion 10 and the transplant Cg face each other when the transplant Cg is taken in. By being combined, the implants Cg can be accommodated collectively in the plurality of needle-like portions 10 . By releasing the implant Cg from each needle-like portion 10, a plurality of implants Cg can be collectively arranged in the target region. Therefore, the efficiency of transplantation is further enhanced.

Specifically, the number and arrangement of the planned placement regions in the tray 50, the number and arrangement of the needle-like portions 10 in the cell transplantation device 100, and the number and arrangement of the outer cylindrical portions 20 are set for one planned arrangement region. It is set so that one needle-like portion 10 and one outer tube portion 20 correspond to each other. Thereby, when the tray 50 and the cell transplantation device 100 face each other along the extension direction, one arrangement planned region, one needle-like portion 10 and one outer tube portion 20 face each other. In other words, one needle-like portion 10 and one outer tube portion 20 are assigned to one planned placement region, and the planned placement region and the needle-like portion 10 correspond one-to-one. There is a one-to-one correspondence between the regions and the outer cylindrical portion 20 .

Since one needle-like part 10 is assigned to one planned placement region, the number of implants Cg to be placed in one planned placement region is adjusted to allow the implant to be incorporated into one needle-like part 10. The number of Cg can be adjusted. Therefore, it is easy to accommodate a certain number of implants Cg in a plurality of needle-like parts 10 . For example, one implant Cg is preferably housed in each needle-like portion 10 .

Note that even when the number of planned placement regions of the tray 50 is one, and the number of the needle-like portion 10 and the number of the outer cylindrical portion 20 of the cell transplantation device 100 are one each, the planned placement region and the needle-like It can be said that one needle-like part 10 and one outer tube part 20 are assigned to one arrangement planned area, if the parts 10 are configured to face each other.

In addition, when the planned arrangement areas of the number and arrangement that match the number and arrangement of the needle-like portions 10 in the cell transplantation device 100 are regarded as one group, the tray 50 may include a plurality of groups of planned arrangement areas. . In such a configuration, the loading of the implant Cg into the cell transplantation device 100 and the placement of the implant Cg in the target region are repeated, and the loading of the implant Cg is performed for each group of placement-planned regions. Thus, even when the tray 50 includes a plurality of groups of planned placement regions, it can be said that one needle-like portion 10 and one outer cylinder 20 are assigned to one planned placement region.

In the above configuration, the cell transplantation device 100 and the tray 50 constitute a biological transfer unit, and the biological transfer device members and the tray 50 constitute a biological transfer kit.

[Modification]
Modified examples of the cell transplantation device 100 will be described in order.
As shown in FIG. 15 , the end surface 12 of the distal end of the needle-like portion 10 is arranged radially inward so as to approach the proximal end of the needle-like portion 10 , in other words, the space inside the needle-like portion 10 . You may have the inclination part 13 which inclines toward. Inclined portion 13 includes a proximal portion of end surface 12 . The proximal end portion of the end surface 12 is a portion including the proximal end of the end surface 12 that is located closest to the proximal end of the needle-like portion 10 in the extending direction. The inclined portion 13 has an angle different from the plane along the opening 11 . Specifically, when the direction connecting the base end and the tip of the end surface 12 is the inclination direction of the opening 11 and the inclination of the inclination direction with respect to the extension direction is positive, the inclination of the inclination portion 13 with respect to the extension direction is negative.

For example, as shown in FIG. 16 , when the end face 12 is viewed from the direction orthogonal to the extending direction, the inclined portion 13 is a region from the proximal end of the end face 12 to the central portion between the distal end and the proximal end. FIG. 15 illustrates a configuration in which the end face 12 has an elliptical ring shape and is composed of three planes. In addition, the range of the inclined portion 13 is not particularly limited, and the inclined portion 13 only needs to include at least the base end portion of the end surface 12 .

If the proximal end of the end face 12 is along the above-mentioned direction of inclination, the structure is such that the proximal end of the end face 12 protrudes toward the opening 11, so that when the implant enters the needle-like portion 10, , may get caught on the proximal end of the end face 12 . The proximal end portion of the end face 12 constitutes an inclined portion 13 , which is inclined toward the space inside the needle-like portion 10 , so that the implant is prevented from being caught on the proximal end portion of the end face 12 . Therefore, the incorporation of the implant into the interior of the needlelike portion 10 is likely to proceed smoothly.

As shown in FIG. 17, the end surface 22 of the distal end portion of the outer cylinder portion 20 may not be flat, and may have unevenness with respect to a plane orthogonal to the extending direction. The unevenness is arranged along the circumferential direction of the outer cylindrical portion 20 . If the end surface 22 has such an uneven structure, even if the end surface 22 is brought into contact with the portion of the tray 50 that holds the transplant, the surface of the tray 50 and the end surface 22 will not be in contact with each other. A gap is formed between the concave portion of the Therefore, since the protective liquid flows into the outer cylindrical portion 20 through the gap, the suction can be continued. Therefore, the uptake of the implant can proceed smoothly.

The length Lt of the opening 21 of the outer cylindrical portion 20 is the length from the distal end to the proximal end of the opening 21 in the extension direction. is smaller than the length Ln of the opening 11 of the needle-like portion 10 .

As described above, according to the biological transfer device of this embodiment, the following effects can be obtained.
(1) By using the cell transplantation device 100, it is possible to continuously perform the process from taking out the transplant from the tray 50 to placing it in the living body with a single device, so smooth transplantation of the transplant is possible. .

(2) By taking in the graft in a state in which the distal end of the outer tube portion 20 protrudes beyond the distal end of the needle-like portion 10, the cylindrical portion into which the graft is taken is brought closer to the graft. can take things in. Therefore, the implant can be easily inserted into the tubular portion, and as a result, the implant can be smoothly taken into the interior of the needle-like portion 10 . Therefore, smoother transplantation is possible.

(3) In a configuration in which the end surface 22 of the distal end portion of the outer cylindrical portion 20 is a plane perpendicular to the direction in which the needle-like portion 10 extends, when the implant is taken in, the tubular portion into which the implant is taken is pushed by the implant. can get closer. Therefore, the implant can be incorporated more smoothly.

(4) In the configuration in which the end surface 22 of the distal end portion of the outer cylinder portion 20 has unevenness with respect to a plane perpendicular to the direction in which the needle-shaped portion 10 extends, the distal end portion of the outer cylinder portion 20 is placed on the tray 50 when the implant is taken in. Even if they are brought into contact with each other, the suction can be continued. Therefore, the uptake of the implant can proceed smoothly.

(5) If the end surface 12 at the distal end of the needle-like portion 10 includes the inclined portion 13 and the proximal portion of the end surface 12 is included in the inclined portion 13, the implant may be placed on the end surface 12 when the implant is taken in. It is possible to prevent catching.

(6) If the inner peripheral surface of the needle-shaped portion 10 and the inner peripheral surface of the outer cylinder portion 20 are configured from a material that suppresses the adhesion of the implant, the implant inside the outer cylinder portion 20 Objects tend to flow into the needle-like portion 10, and the implant tends to exit the needle-like portion 10 when the implant is placed in the target area. Therefore, transplantation can proceed more smoothly.

(7) The distal end portion of the needle-like portion 10 is exposed from the outer tube portion 20 by sliding the outer tube portion 20 relative to the needle-like portion 10 . Therefore, since the movement of the outer cylinder part 20 for exposing the tip part of the needle-like part 10 can be easily performed, after the implant is taken into the inside of the needle-like part 10, the implant can be rapidly delivered to the target region. can be placed. Therefore, deterioration of the implant can be suppressed.

(other forms)
The embodiment and modifications described above can be modified and implemented as follows.
- The inner diameter of the outer cylinder part 20 may not be constant. For example, the inner diameter of the distal end portion of the outer cylinder portion 20 may gradually expand toward the end face 22 within a range in which the suction force is maintained. With such a configuration, a large opening 21 can be secured, so that the implant can easily enter the opening 21 .

Alternatively, as shown in FIG. 18, the inner diameter of the portion of the outer cylinder 20 that is located on the distal side of the end surface 12 of the distal end of the needle-like portion 10 when the graft is taken in is equal to the inner diameter of the needle-like portion 10. , and the inner diameter of the outer tube 20 may be changed so that the inner diameter of the portion surrounding the needle 10 is greater than or equal to the outer diameter of the needle 10 when the implant is taken in. In other words, the inner peripheral surface of the outer barrel 20 has a stepped portion 23 along the end surface 12 of the needle 10 when attached to the needle 10 during implant uptake. In FIG. 18, the end face 12 of the needle-like portion 10 and the stepped portion 23 are shown separated for easy understanding, but they are arranged so as to be in contact with each other when taking in the implant. be done. According to such a configuration, the diameter of the channel through which the implant passes is constant from the inside of the outer tube portion 20 to the inside of the needle-like portion 10 , and no step is formed on the end surface 12 . It is possible to prevent catching. In addition, the outer shape of the outer cylindrical portion 20 may be constant, or may change according to the inner diameter.

- The end surface 22 of the outer cylinder part 20 may be inclined with respect to the extending direction, that is, the length Lt of the opening 21 along the extending direction may not be zero. If the length Lt of the opening 21 is smaller than the length Ln of the opening 11 of the needle-like portion 10, when the implant is taken in, the cylindrical shape into which the implant can be taken in is greater than the case where the outer tube portion 20 is not provided. can be brought closer to the implant.

- At least a portion of the outer tube portion 20 may be elastically deformable or plastically deformable. Moreover, the outer cylinder part 20 may have an elastically deformable portion and a plastically deformable portion. For example, as shown in FIG. 19, if the portion of the outer tube 20 that protrudes beyond the distal end of the needle-like portion 10 when taking in an implant includes a deformable portion, the outer tube Section 20 can be deformed to bring its tip closer to implant Cg. Therefore, since the degree of freedom of the positional relationship between the needle-like portion 10 and the implant is increased when the implant is taken in, it is also possible to facilitate the take-in of the implant.

- As long as the needle-like portion 10 has an opening 11 at the distal end thereof, which serves as an inlet and an outlet for the implant, other structures may be different from those of the above-described embodiment. For example, the internal space of the needle-like portion 10 may extend in a direction inclined with respect to the extending direction. In addition, the cylindrical member, which is the needle-like portion 10 and the outer cylindrical portion 20, has openings at the distal end portion and the proximal end portion, and these openings communicate through the space inside the cylinder. It is not limited to a structure extending cylindrically. If the length Lt of the opening 21 of the outer tube portion 20 in the extending direction is smaller than the length Ln of the opening 11 of the needle-like portion 10, the outer shape of the tubular member and the inside of the tubular member are partitioned. The shape of the space to be formed may be cylindrical, pyramidal, or prismatic, and is not particularly limited. Moreover, the needle-like part 10 may have a structure for fixing the implant in the region from the middle of the extension direction to the distal end in the internal space. For example, the flow of the implant to the proximal side of the predetermined position in the internal space may be suppressed by changing the cross-sectional area in the internal space or by arranging a filter or a mesh-like structure.

A state in which a tubular portion is arranged inside the needle-shaped portion 10 instead of the outer tubular portion 20, and the tip of the tubular portion protrudes from the tip of the needle-shaped portion 10, that is, a tubular shape from the opening 11 Aspiration of the implant may be performed with the distal end of the tube protruding. The implant is held at the distal end portion of the tubular portion so as to block the opening of the distal end portion, or is held in the tubular portion by being drawn into the tubular portion, and the tubular portion is needle-shaped. By being moved with respect to the portion 10, it is taken into the interior of the needle portion 10 together with the distal end portion of the tubular portion. Even with such a configuration, if the length of the opening at the distal end of the tubular portion is smaller than the length of the opening 11 of the needle-like portion 10 in the extending direction, the tubular portion into which the implant is taken in is used. The part can be brought closer to the implant.

- 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 when placed in vivo. For example, the cell group to be transplanted may be a cell group that exerts effects in cosmetic applications such as elimination of wrinkles in the skin and improvement of moisturizing conditions. Furthermore, the object to be transferred into the living body by the biological transfer device is not limited to a group of cells, and may be a solid substance such as a medicine.

(Example)
A cell transplantation device as the above-described biological transfer device will be described using specific examples.

<Example 1>
200 μL of pure water was added to a 96-well plate (Sumitomo Bakelite: prime surface), and plastic beads with a diameter of 210 μm were arranged one by one as a cell group model. A cell transplantation device was prepared which had a 25G injection needle as a needle-like portion and a Teflon transparent tube as an outer cylindrical portion. The outer cylinder part is slidable to the proximal end side of the needle-like part.

A cell transplantation device was used to incorporate the plastic beads that had settled in the 96-well plate. Suction during uptake was performed using a syringe pump under the conditions of rate=1000 μL/min and volume=150 μL. When the plastic beads were taken up 10 times, the plastic beads could be taken up into the needle-like portion in all of the 10 times. When the outer cylinder part was removed from the needle-shaped part and the plastic beads were taken in in the same manner, the plastic beads could not be taken into the needle-shaped part in all of the 10 times.

<Example 2>
200 μL of dermal papilla cell growth medium (PromoCell) was added to a 96-well plate (Sumitomo Bakelite: prime surface), and 4×10 ³ cells of human dermal papilla cells (PromoCell) were seeded. Culture was performed for 72 hours in an atmosphere of 5% CO ₂ and 37°C. After culturing, it was confirmed that cell aggregates with a diameter of about 200 μm were formed.

Using the same cell transplantation device as in Example 1, cell masses precipitated in a 96-well plate were incorporated. Suction during uptake was performed using a syringe pump under conditions of rate=500 μL/min and volume=150 μL. When the uptake of the cell mass was performed 10 times, the cell mass could be taken into the needle-like portion in all of the 10 times. When the outer cylinder part was removed from the needle-shaped part and the cell masses were taken up in the same manner, the cell masses could not be taken into the needle-shaped part in all of the 10 times.

<Example 3>
For the cell transplantation device used in Examples 1 and 2, the outer cylinder was moved to the base end side of the needle-like portion to expose the tip portion of the needle-like portion. The length of the tip of the exposed needle is 5 mm. When the skin of the excised nude mouse (manufactured by Japan Charles River Co., Ltd.) was pierced with the needle, the needle was able to penetrate into the skin.

DESCRIPTION OF SYMBOLS 10... Needle-shaped part 11... Opening 12... End face 13... Inclined part 20... Outer cylinder part 21... Opening 22... End face 30... Support part 40... Suction part 50... Tray 51... Recessed part , 100... Cell transplantation device.

Claims (9)

A living body transfer device for placing an object in a living body,
a cylindrical needle-like portion extending along one direction, the needle-like portion taking in the object from an opening positioned at the tip of the needle-like portion;
Along the direction in which the needle-like portion extends from a state in which the tip of the tube-like portion is located outside the needle-like portion and protrudes beyond the tip of the needle-like portion. and the cylindrical portion configured to be movable,
In the direction in which the needle-like part extends, the length of the opening positioned at the distal end of the cylindrical part is smaller than the length of the opening positioned at the distal end of the needle-like part. The biological transfer device according to claim 1, wherein the end surface provided at the tip of the tubular portion is a plane perpendicular to the direction in which the needle-like portion extends. 2. The biological transfer device according to claim 1, wherein the end surface of the tip of the tubular portion has unevenness with respect to a plane perpendicular to the direction in which the needle-like portion extends. The end surface provided at the distal end of the needle-like portion includes an inclined portion that is inclined inward in the radial direction so as to approach the base end of the needle-like portion,
The biological transfer device according to any one of claims 1 to 3, wherein the inclined portion includes a base end portion of the end surface in the extending direction of the needle-like portion. At least one of the inner peripheral surface of the needle-shaped portion and the inner peripheral surface of the cylindrical portion is made of a material that suppresses adhesion of the object according to any one of claims 1 to 4. Living body transfer device. The biological transfer device according to any one of claims 1 to 5 , wherein the tubular portion is configured to be slidable along the outer peripheral surface of the needle portion. A member that is attached to a device that has a cylindrical needle-like part that extends along one direction, takes in an object through an opening positioned at the tip of the needle-like part, and places the object in a living body. and
A cylindrical portion fitted to the outside of the needle-like portion and configured to be slidable along the outer peripheral surface of the needle-like portion,
In the extending direction of the needle-shaped part, the length of the opening positioned at the distal end of the tubular part is smaller than the length of the opening positioned at the distal end of the needle-shaped part. a tray having one or more planned placement regions, which are regions where objects are to be placed;
a biological transfer unit for transferring the object from the tray into the living body,
The biological transfer device is
a cylindrical needle-shaped portion extending along one direction, the needle-shaped portion taking in the object located in the planned arrangement area from an opening located at the tip of the needle-shaped portion;
Along the direction in which the needle-like portion extends from a state in which the tip of the tube-like portion is located outside the needle-like portion and protrudes beyond the tip of the needle-like portion. and the cylindrical portion configured to be movable,
One needle-shaped portion is assigned to one of the planned placement regions,
In the extending direction of the needle-shaped part, the length of the opening positioned at the distal end of the tubular part is smaller than the length of the opening positioned at the distal end of the needle-shaped part. a tray having a plurality of planned placement regions, which are regions where objects are to be placed;
A cylindrical needle-like portion extending along one direction is provided, and the object located in the arrangement planned region is taken into the inside from an opening located at the tip of the needle-like portion, and is introduced into the living body from the tray. and a member attached to the device for transferring the object,
The member includes a plurality of tubular portions that are fitted to the outside of the needle-shaped portion and configured to be slidable along the outer peripheral surface of the needle-shaped portion. the length of the opening located at the distal end of the needle-shaped portion is smaller than the length of the opening located at the distal end of the needle-shaped portion;
A transport kit for a living body, wherein one tubular portion is assigned to one planned placement region.

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