Cell transplantation kit and cell transplantation device

Abstract

To provide a cell transplantation kit, a cell transplantation device, and a transplant taking-in method capable of protecting a cell group from external force attributed to an operation for transplantation.SOLUTION: A cell transplantation kit includes a transplant 10 including a cell group 11 and a cell transplantation device. The cell transplantation device includes a needle-like part 30 extending in a cylindrical manner and a suction part for sucking the inside of the needle-like part 30. The needle-like part 30 is configured so as to attract the transplant 10 by sucking, and take in the transplant 10 inside from an opening 33 at the tip of the needle-like part 30. In a state in which the transplant 10 is taken in, the inner diameter of the needle-like part 30 becomes smaller on the way from the tip to the base end of the needle-like part 30. The suction pressure of the suction part is -100 kPa or more to -0.1 kPa or less. The transplant 10 includes a gelatinous protection part 12 for covering at least part of the cell group 11. The outer diameter of the transplant 10 is equal to or larger than the minimum value of the inner diameter of the needle-like part 30, and the jelly strength of the protection part 12 is 100 g or more.SELECTED DRAWING: Figure 8

Description

[Technical field]

[0001] The present invention relates to a cell transplantation kit, and, cell transplant device Place Regarding. [Background technology]

[0002] The use of technology for transplanting cell groups into living organisms is progressing. For example, attempts have been made to regenerate hair by culturing cell groups that contribute to the formation of hair follicles, which are organs that produce hair, and transplanting the cell groups into the skin. For successful hair regeneration, it is desirable for hair follicles that have a normal tissue structure and a good ability to form hair to be generated from the transplanted cell groups. Thus, various research and development efforts have been conducted on methods for producing cell groups capable of forming such hair follicles (see, for example, Patent Documents 1 to 3). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2017 / 073625 [Patent Document 2] International Publication No. 2012 / 108069 [Patent Document 3] JP 2008-29331 A Summary of the Invention [Problem to be solved by the invention]

[0004] When transplanting a cell group, an external force may be applied to the cell group due to the operation of the cell group. For example, the cell group may come into contact with an instrument for transporting the cell group from a culture vessel to a living body, and the cell group may be subjected to a pressing force from the instrument. If the influence of such an external force on the cell group becomes large, the cell group may undergo mutations such as collapse, which may reduce the efficiency and success rate of transplantation.

[0005] The present invention provides a cell transplantation kit capable of protecting a cell population from external forces caused by transplantation procedures, and, cell transplant device Place The purpose is to provide. [Means for solving the problem]

[0006] A cell transplantation kit for solving the above problem is a cell transplantation kit comprising a transplant containing a cell group and a cell transplantation device for placing the transplant inside a living body, the cell transplantation device comprising a needle-shaped portion extending in a cylindrical shape and a suction portion which suctions inside the needle-shaped portion, the needle-shaped portion is configured to attract the transplant by suction with the suction portion and to be able to take the transplant inside from an opening at the tip of the needle-shaped portion, and when the transplant has been taken in, the inner diameter of the needle-shaped portion becomes smaller on the way from the tip to the base end of the needle-shaped portion, the suction pressure formed by the suction portion is -100 kPa or more and -0.1 kPa or less, the transplant includes a protective portion which covers at least a portion of the cell group, the outer diameter of the transplant is equal to or greater than the minimum value of the inner diameter of the needle-shaped portion, and the jelly strength of the protective portion is 100 g or more.

[0007] According to the above configuration, since the cell group is covered by the protective part, it is possible to protect the cell group from external forces that the transplant receives due to contact between the cell transplantation device and the transplant, and to prevent the cell group from being deformed, such as collapse. Furthermore, if the suction pressure is within the above range, the transplant can be attracted to the needle-shaped part by suction while suppressing deformation of the transplant, and the transplant can be taken into the needle-shaped part.

[0008] In the above configuration, the needle-shaped portion has a container portion that communicates with the opening and in which the implant that has been taken in is contained, and the outer diameter of the implant may be 2.5 times or less the inner diameter of the container portion.

[0009] According to the above configuration, the transplant can be smoothly accommodated in the accommodation section. In addition, since the needle-shaped part can take in a transplant with an outer diameter larger than the inner diameter of the accommodation section, a large transplant can be transplanted while suppressing the enlargement of the outer diameter of the needle-shaped part. Therefore, it is possible to improve the ease with which the needle-shaped part can be inserted into the living body, reduce the burden on the living body caused by the needle-shaped part being inserted, and promote the growth and engraftment of the cell group.

[0010] In the above configuration, the outer diameter of the implant may be 2.8 times or more the minimum value of the inner diameter of the needle-shaped portion. According to the above-mentioned configuration, the transplant is retained in the needle-shaped portion midway from the tip to the base end, so that the incorporation and release of the transplant into the needle-shaped portion can be smoothly carried out.

[0011] In the above configuration, the protective portion may include an extracellular matrix. According to the above configuration, the protective part can preferably protect the cell group, and the suitability of the transplant for placement in a living body is improved.

[0012] In the aforementioned configuration, the protective portion may include collagen. According to the above configuration, when a transplant is transplanted onto the skin, the biocompatibility of the protective part is suitably improved.

[0013] In the above configuration, the needle-shaped portion has an outer tube portion that extends cylindrically and has the opening, and an inner tube portion that extends cylindrically inside the outer tube portion, and the inner tube portion is configured to be movable relative to the outer tube portion between a position where the tip of the inner tube portion is located inside the outer tube portion and a position where the tip of the inner tube portion protrudes from the opening of the outer tube portion, and the suction portion may suck inside the inner tube portion, and the implant may be held at the tip of the inner tube portion by the suction.

[0014] According to the above-mentioned configuration, the tip of the inner tube part is protruding from the opening of the outer tube part, and the transplant can be held at the tip of the inner tube part by suctioning the inside of the inner tube part. Therefore, the transplant to be taken in can be accurately captured and taken in the needle-shaped part.

[0015] In the above configuration, the cell group may include hair follicle primordium. Hair follicle primordia have a structure in which an aggregated portion of mesenchymal cells and an aggregated portion of epithelial cells are adjacent to each other, and therefore often have a shape other than an approximately spherical shape. Therefore, since a weak spot is easily formed locally in the cell group, the cell group is easily collapsed by an external force in the absence of a protective part. In addition, if either the aggregated portion of mesenchymal cells or the aggregated portion of epithelial cells is destroyed, the function as the primordium is lost, so the collapse of the cell group has a greater impact on the function of the cell group compared to a cell group in which the same type of cells are gathered. Therefore, the effect of protecting the transplant by the protective part is highly obtained.

[0016] A cell transplantation device for solving the above problems is a cell transplantation device for placing a transplant including a cell group and a gel-like protective part covering at least a portion of the cell group into a living body, the cell transplantation device comprising: a needle-shaped part having an outer tube part extending in a cylindrical shape and an inner tube part extending in a cylindrical shape inside the outer tube part; and a suction part which suctions the inside of the inner tube part, the needle-shaped part is configured to hold the transplant at the tip of the inner tube part by suction with the suction part, and to be able to take the transplant into the needle-shaped part through an opening at the tip of the outer tube part, and the suction pressure formed by the suction part is -100 kPa or more and -0.1 kPa or less.

[0017] According to the above configuration, since the cell group is covered by the protective part, it is possible to protect the cell group from external forces that the transplant receives due to contact between the cell transplantation device and the transplant, and to prevent the cell group from being deformed, etc. Furthermore, if the suction pressure is within the above range, the transplant can be held at the tip of the inner tube by suction while suppressing deformation of the transplant, and the transplant can be taken into the needle-shaped part.

[0018] A method of incorporating a transplant to solve the above problem is a method of incorporating a transplant into a cell transplantation device for placing the transplant in a living body, the transplant including a cell group and a gel-like protective part covering at least a part of the cell group, the cell transplantation device including a needle-shaped part extending in a cylindrical shape and a suction part that suctions the inside of the needle-shaped part by suction with the suction part, and incorporating the transplant inside through an opening at the tip of the needle-shaped part so that the suction pressure P (kPa) generated by the suction part and the jelly strength I (g) of the protective part satisfy the following formula (1): -1.0≦P / I (1) According to the above method, mutations such as collapse of the cell population caused by the uptake of the transplant into the cell transplantation device using suction can be suppressed.

[0019] The method may include forming the protective portion to prepare the implant. According to the above method, by adjusting the jelly strength by the material of the protective part in the transplant preparation step and by adjusting the suction pressure in the transplant introduction step, it is possible to preferably realize the introduction of the transplant that satisfies the above formula (1). Effect of the Invention

[0020] According to the present invention, a cell population can be protected from external forces caused by procedures for transplantation. [Brief description of the drawings]

[0021] [Figure 1] FIG. 2 is a diagram showing an example of a transplant provided in a cell transplantation kit of one embodiment. [Diagram 2] FIG. 2 is a diagram showing an example of a transplant provided in a cell transplant kit of one embodiment. [Diagram 3] FIG. 2 is a diagram showing an example of a transplant provided in a cell transplant kit of one embodiment. [Figure 4] FIG. 1 is a diagram showing the configuration of a cell transplantation device according to one embodiment. [Diagram 5] FIG. 2 is a diagram showing a cross-sectional structure of a needle-shaped part provided in one embodiment of the cell transplantation device. [Figure 6]FIG. 13 shows the needle prior to holding the implant according to one embodiment of the implant loading method. [Figure 7] FIG. 13 is a diagram showing a state in which a transplant is held at the tip of the inner tube of the needle-shaped part, in accordance with one embodiment of the method for incorporating a transplant. [Figure 8] FIG. 13 is a diagram showing the state in which a transplant has been incorporated inside the needle-shaped part, in accordance with one embodiment of the method for incorporating a transplant. [Figure 9] FIG. 13 is a diagram showing the state in which the needle-shaped portion is inserted into the living body, in accordance with one embodiment of the method for placing the implant. [Figure 10] FIG. 13 is a diagram showing a state in which the inner tube part has been moved relative to the outer tube part in one embodiment of a method for placing an implant. [Figure 11] FIG. 13 is a diagram showing a state in which the needle-shaped portion has been removed from the living body, in accordance with one embodiment of the method for placing the implant. [Figure 12] FIG. 13 is a diagram showing a cross-sectional structure of a needle-shaped portion according to a modified example. [Figure 13] FIG. 13 shows a stained cross-sectional image of an example of an implant. [Figure 14] FIG. 13 shows a stained cross-sectional image of an example of an implant. [Figure 15] FIG. 13 shows a stained cross-sectional image of an example of an implant. [Figure 16] FIG. 13 shows an image of the appearance of an example implant released after incorporation into a cell transplantation device. [Figure 17] FIG. 13 shows an image of the appearance of a comparative example implant released after incorporation into a cell transplantation device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] An embodiment of a cell transplantation kit, a cell transplantation device, and a method for incorporating a transplant will be described with reference to FIGS. The cell transplantation kit of this embodiment includes a transplant and a cell transplantation device used to transport and place the transplant in a living body. The target area of ​​transplantation in a living body is at least one of intradermal and subcutaneous, or in tissues such as an organ. In this embodiment, the "living body" includes not only the body and tissues of an organism, but also an artificial living body model that imitates the body and tissues. In other words, the cell transplantation device of this embodiment can transport and place the transplant not only in an organism, but also in a living body model. Below, the transplant, the cell transplantation device, and the method of incorporating the transplant into the cell transplantation device will be described in order.

[0023] [Transplant] As shown in FIG. 1, the implant 10 includes a cell group 11 and a protective portion 12 that covers the cell group 11.

[0024] The cell group 11 includes a plurality of cells. The cell group 11 may be an aggregate of a plurality of aggregated cells, or an aggregate of a plurality of cells bound by intercellular bonds. Alternatively, the cell group 11 may be composed of a plurality of dispersed cells. The cells constituting the cell group 11 may be undifferentiated cells, or may be cells in which differentiation has been completed, or the cell group 11 may include undifferentiated cells and differentiated cells. The cell group 11 is, for example, a cell mass (spheroid), an anlage, tissue, organ, organoid, mini-sized organ, etc.

[0025] The cell group 11 has the ability to affect tissue formation in a living body by being placed in a target area for transplantation in the living body. One example of the cell group 11 having such an ability is a cell aggregate containing cells having stem cell properties.

[0026] The cell group 11 contributes to hair growth or hair development, for example, by being placed intradermally or subcutaneously. Such cell group 11 has 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, or the ability to induce or promote the formation of hair in a hair follicle. The cell group 11 may also include cells that contribute to the control of hair color, such as pigment cells or stem cells that differentiate into pigment cells. The cell group 11 may also include vascular cells.

[0027] A specific example of the cell group 11 in this embodiment is a hair follicle primordium, which is a primitive hair follicle organ. The hair follicle primordium includes mesenchymal cells and epithelial cells. In the hair follicle organ, hair papilla cells, which are mesenchymal cells, induce the differentiation of hair follicle epithelial stem cells, and hair matrix cells repeatedly divide in the hair bulb portion thus formed, thereby forming hair. The hair follicle primordium is a cell group that differentiates into such a hair follicle organ.

[0028] The hair follicle primordium is formed, for example, by co-culturing mesenchymal cells derived from mesenchymal tissue such as the hair papilla and epithelial cells derived from epithelial tissue located in the bulge region, hair bulb base, etc. under a predetermined condition. However, the method for producing the hair follicle primordium is not limited to the above-mentioned example. In addition, the origin of the mesenchymal cells and epithelial cells used for producing the hair follicle primordium is not limited, and these cells may be cells derived from the hair follicle organ, cells derived from an organ different from the hair follicle organ, or cells induced from pluripotent stem cells.

[0029] The protective part 12 is a gel composition, specifically, a hydrogel. The main component of the protective part 12 is a hydrophilic polymer. The hydrophilic polymer contained in the protective part 12 may be a naturally derived polymer, an artificially synthesized polymer, or a mixture of a naturally derived polymer and an artificially synthesized polymer, but among them, a naturally derived polymer is preferable. In addition, the hydrophilic polymer contained in the protective part 12 is preferably a polymer having biocompatibility. Biocompatibility means that it does not cause a reaction such as severe inflammation when it comes into contact with a living body. From these viewpoints, the hydrophilic polymer contained in the protective part 12 is most preferably an extracellular matrix. As long as it is a substance that can exist in a living body as an extracellular matrix, the type is not particularly limited and it can be used as the material of the protective part 12.

[0030] Specific examples of naturally occurring polymers among the materials of the protective part 12 include collagen (e.g., type I, type II, type III, type IV, type V, and type VI), carboxymethylcellulose, fibronectin, laminin, elastin, glycosaminoglycan, proteoglycan, fibrin, gelatin, agar, agarose, and sodium alginate. Specific examples of artificially synthesized polymers include polyacrylamide, polyvinyl alcohol, methylcellulose, and polyethylene oxide. Examples of products that can be used as the material of the protective part 12 include Matrigel (manufactured by Corning, registered trademark), Cell Matrix (manufactured by Nitta Gelatin, registered trademark), and Mebiol Gel (manufactured by Ikeda Rika Co., Ltd., Mebiol Co., Ltd., registered trademark). The above materials may be used alone or in combination.

[0031] Among the above materials, type I collagen is preferably used as the material of the protective part 12. The type I collagen may be derived from humans or animals other than humans. Specific examples of animals other than humans include pigs, cows, horses, and chickens.

[0032] The strength of the protective part 12 is represented by the jelly strength defined in JIS K6503. The jelly strength of the protective part 12 is preferably 100 g or more. If the jelly strength of the protective part 12 is 100 g or more, the protective part 12 can provide a good function of protecting the cell group 11. In order to enhance the protective function, the jelly strength of the protective part 12 is preferably 150 g or more. There is no particular upper limit to the jelly strength of the protective part 12, but from the viewpoint of facilitating the formation of the protective part 12, the jelly strength of the protective part 12 is preferably 300 g or less.

[0033] The jelly strength of the protective part 12 can be adjusted by the type and composition of the material of the protective part 12. For example, when collagen is used as the material of the protective part 12, in order to obtain a jelly strength within the above range, the concentration of the collagen solution used to form the protective part 12 is preferably 1.5 mg / ml or more, and more preferably 2.0 mg / ml or more.

[0034] The protective part 12 may contain a promoting factor for promoting the growth and engraftment of the cell group 11. Examples of promoting factors include insulin, EGF, FGF, IGF, N-2 Supplement and Revita Cell Supplement manufactured by Thermo Fisher Scientific, RSPO1, Noggin, ROCK-inhibitors (e.g., Y27632, HA-1077), GSK-3β inhibitors (e.g., SB-216763, BIO, CHIR99021, CHIR98014, TWS119), anti-inflammatory agents (e.g., Dexamethasone, Prednisolone, Methylprednisolone, Triamicinolone, Betamethasone, Cortisol, acetylsalicylic acid, Ibuprofen, Loxoprofen, Diclofenac), PD0325901, RepSox, PluriSln#1, and TNF-α. The protective part 12 may contain only one type of the promotion factor, or may contain two or more types of the promotion factors. Additionally, the protective portion 12 may contain an antibiotic to inhibit bacterial growth.

[0035] The protective part 12 may be colorless and transparent, or may be colored. When the protective part 12 is colorless and transparent, it is easy to observe the cell group 11 during the formation of the transplant 10. On the other hand, when the protective part 12 is colored, the visibility of the transplant 10 is improved, and therefore it is easy to confirm the position of the transplant 10 when the transplant 10 is taken into or released from the cell transplantation device.

[0036] By covering the cell group 11 with the protective part 12, it is possible to protect the cell group 11 from external forces applied to the transplant 10. In order to enhance the protective function of the protective part 12, it is preferable that the protective part 12 covers the entire cell group 11. However, if at least a part of the cell group 11 is covered with the protective part 12, it is possible to protect the cell group 11 from external forces compared to a case in which the entire cell group 11 is not covered with the protective part 12.

[0037] In the transplant 10, the cell group 11 may be one mass or may be divided into multiple masses. When the cell group 11 is composed of multiple dispersed cells, the cells are dispersed in the protective part 12. The transplant 10 may contain dispersed cells in addition to the aggregated cell group 11.

[0038] When the cell group 11 contributes to hair growth or hair development, the cell group 11 is cultured so that one clump of cell group 11 corresponds to one hair follicle organ, and transplantation is performed so that one transplant 10 is placed at the position where one hair follicle organ develops, which makes it easy to control the distribution of the growing hair. That is, it is preferable that the cell group 11 is in the form of one clump in the transplant 10. When the cell group 11 is a hair follicle primordium, the cell group 11 is in the form of one clump in the transplant 10.

[0039] When the cell group 11 is in the form of a single mass, the outer diameter dc of the cell group 11 is, for example, 50 μm or more and 1000 μm or less. From the viewpoint of reducing the burden required for culturing the cell group 11 and increasing the engraftment rate of the cell group 11, the outer diameter dc is preferably 100 μm or more and 800 μm or less. The outer diameter dc of the cell group 11 is the diameter of a sphere when the cell group 11 is approximated to a sphere, in other words, the diameter of the smallest sphere circumscribing the cell group 11.

[0040] The outer diameter do of the implant 10 is, for example, greater than 50 μm and equal to or less than 3 mm. The outer diameter do of the implant 10 is determined according to the size of the cell group 11 and the thickness of the protective part 12. The outer diameter do of the implant 10 is the diameter of a sphere when the implant 10 is approximated to a sphere, in other words, the diameter of the smallest sphere circumscribing the implant 10.

[0041] When the cell group 11 is in the form of a single mass, the thickness t of the protective part 12 is the length from the surface of the cell group 11 to the surface of the protective part 12 in a direction along the diameter of the smallest sphere circumscribing the implant 10. The thickness t of the protective part 12 may be determined according to the level of protective function required of the protective part 12. The greater the thickness t, the higher the protective function of the protective part 12 for the cell group 11. From the viewpoint of ensuring oxygen permeability and nutrient permeability in the protective part 12 and promoting the growth of the cell group 11, it is preferable that the thickness t is equal to or less than the outer diameter dc of the cell group 11.

[0042] The thickness t may be uniform or non-uniform around the cell group 11. For example, when the strength of the cell group 11 varies depending on the part of the cell group 11, the thickness t of the part of the protective part 12 that covers the part of the cell group 11 that has low strength may be made larger than the thickness t of the other parts. This allows the protection of the part of the cell group 11 that has low strength to be focused on.

[0043] The outer diameter do of the implant 10 is measured by observing the entire implant 10 under a microscope. When the protective part 12 is transparent, it is possible to distinguish the boundary between the cell group 11 and the protective part 12 by transmission observation, and therefore each of the outer diameter dc of the cell group 11 and the thickness t of the protective part 12 can also be measured by observation using a microscope.

[0044] When the cell group 11 is a mass of cells forming a clump, the cell group 11 may have a shape that spreads isotropically from the center, such as a sphere, or may have a shape that spreads anisotropically from the center.

[0045] 2, cell group 11 may have a shape that is constricted at the center, like two roughly spherical masses joined together. The constricted portion is constricted portion 13. Since a hair follicle primordium has a structure in which an aggregate portion of mesenchymal cells and an aggregate portion of epithelial cells are adjacent to each other, when cell group 11 is a hair follicle primordium, cell group 11 may have a shape that is constricted at the center, which is the boundary between the aggregate portions.

[0046] In the example shown in Figure 2, the thickness t of protective part 12 is not constant, and the thickness t is greater in the portion covering constricted portion 13. When cell group 11 has constricted portion 13, the strength of cell group 11 is reduced at constricted portion 13, and cell group 11 is likely to collapse from constricted portion 13 in response to an external force. Because the thickness t of protective part 12 is greater at the position of constricted portion 13, impacts due to external forces are prevented from reaching constricted portion 13, allowing cell group 11 to be appropriately protected. Even if the cell group 11 has a distorted shape, the outer diameter dc of the cell group 11 is the diameter of the smallest sphere that circumscribes the cell group 11.

[0047] In the example shown in Figure 3, cell group 11 has a shape in which two small clusters are joined to one large cluster. The part corresponding to the large cluster is large cluster portion 14, and the part corresponding to the small cluster is small cluster portion 15. The two small cluster portions 15 are adjacent to each other.

[0048] 3, protective portion 12 covers cell group 11 only around two small masses 15, and does not cover the entire cell group 11. While protective portion 12 covers the entire two small masses 15 and the boundary between large mass 14 and small mass 15, part of large mass 14 is exposed from protective portion 12.

[0049] When cell group 11 has a structure consisting of large clumps 14 and small clumps 15, the strength of cell group 11 is reduced around small clumps 15, such as the boundary between large clumps 14 and small clumps 15, and cell group 11 is prone to collapse from the periphery of small clumps 15 in response to an external force. Small clumps 15 and the boundary between large clumps 14 and small clumps 15 are covered by protective section 12, allowing cell group 11 to be protected appropriately. Even if the implant 10 has a distorted shape, the outer diameter do of the implant 10 is the diameter of the smallest sphere that circumscribes the implant 10 .

[0050] There is no particular limitation on the method for forming the transplant 10, i.e., the method for covering the cell group 11 with the protective part 12. For example, the transplant 10 can be formed by suspending cells in a hydrogel that will become the protective part 12 and forming the cell group 11 in the hydrogel, applying the hydrogel that will become the protective part 12 to the cell group 11, or embedding the cell group 11 in the hydrogel that will become the protective part 12. In addition to the cell group 11 and the protective part 12, the transplant 10 may include a member that assists in the placement of the cell group 11 in the living body.

[0051] [Cell transplant device] 4, the cell transplantation device 20 includes a needle-shaped portion 30 extending in one direction, and a support portion 40 that supports the needle-shaped portion 30. The needle-shaped portion 30 includes an outer tube portion 31 that extends in a cylindrical shape, and an inner tube portion 32 that extends in a cylindrical shape inside the outer tube portion 31. That is, the needle-shaped portion 30 has a double cylindrical shape.

[0052] As long as the tip of the outer tube part 31 has a shape that allows it to pierce the target site of transplantation in a living body, there is no particular limitation on the other shapes of the outer tube part 31. For example, the outer tube part 31 extends in a cylindrical shape, and the tip of the outer tube part 31 has a shape obtained by cutting a cylinder obliquely with respect to the extending direction, and is sharp.

[0053] The inner cylinder portion 32 is not particularly limited in shape as long as it is cylindrical. For example, when the outer cylinder portion 31 extends cylindrically, the inner cylinder portion 32 may also extend cylindrically. It is preferable that the end surface of the tip of the inner cylinder portion 32 is a plane perpendicular to the extension direction of the inner cylinder portion 32.

[0054] The support part 40 may be formed integrally with the outer tube part 31, or may be a member formed separately from the outer tube part 31. The outer shape of the support part 40 is not particularly limited. When the support part 40 is formed integrally with the outer tube part 31, the outer tube part 31 protrudes from the support part 40.

[0055] When the support part 40 is a member formed separately from the outer tube part 31, the support part 40 surrounds the outside of the outer tube part 31 except for the tip part and its vicinity, and supports the outer tube part 31. For example, the needle-shaped part 30 is attached to the support part 40 by passing the needle-shaped part 30 through a hole in the support part 40. The tip part and its vicinity of the outer tube part 31 protrude from the support part 40 along the extension direction of the needle-shaped part 30.

[0056] Regardless of whether the outer tube portion 31 and the support portion 40 are separate members or formed integrally, the portion of the outer tube portion 31 protruding from the support portion 40 includes at least a portion that penetrates into the target area of ​​transplantation in the living body. The outer tube portion 31, the inner tube portion 32, and the support portion 40 are formed from metal or resin. The outer tube portion 31 is formed from a material that has the strength to pierce the target area of ​​transplantation in the living body.

[0057] The cell transplantation device 20 further includes a suction section 50 that suctions the inside of the needle-shaped portion 30, and a position change section 60 that includes a mechanism for moving the inner tube portion 32 relative to the outer tube portion 31 along the extension direction of the needle-shaped portion 30.

[0058] The suction unit 50 has a mechanism for sucking in air by the movement of a pump, a piston, or the like. The suction unit 50 is connected to the inner cylinder portion 32 and sucks the inside of the inner cylinder portion 32. The suction unit 50 may be incorporated inside the support portion 40, or may be provided outside the support portion 40 and connected to the inner cylinder portion 32 through the inside of the support portion 40.

[0059] By actuation of the position changing unit 60, the inner tube portion 32 is moved relative to the outer tube portion 31 between a position where the tip portion of the inner tube portion 32 is disposed inside the outer tube portion 31 and a position where the tip portion of the inner tube portion 32 protrudes from an opening 33 at the tip portion of the outer tube portion 31. The state where the tip portion of the inner tube portion 32 is disposed inside the outer tube portion 31 is a first state of the needle-shaped portion 30, and the state where the tip portion of the inner tube portion 32 protrudes from the opening 33 is a second state of the needle-shaped portion 30.

[0060] The position changer 60 includes members for pushing and pulling the outer cylinder 31 and the inner cylinder 32. The position changer 60 may be operated manually, or may include electronic components such as a motor and the position changer 60 may be operated electrically. The position changer 60 may be incorporated inside the support 40, or may be provided outside the support 40 and connected to the outer cylinder 31 and the inner cylinder 32 through the inside of the support 40.

[0061] In addition to the above-mentioned components, the cell transplantation device 20 may have a member for determining the depth at which the transplant 10 is placed in the target site of transplantation. For example, the cell transplantation device 20 may have a stopper or a scale for regulating the depth at which the needle-shaped portion 30 is inserted into the target site of transplantation.

[0062] The internal structure of the needle-shaped part 30 will be further described with reference to Fig. 5. In a first state in which the tip of the inner cylinder part 32 is located inside the outer cylinder part 31, the tubular part between the tip of the inner cylinder part 32 and the tip of the outer cylinder part 31 is a housing part 34 in which the transplant 10 is housed. The housing part 34 communicates with an opening 33 of the outer cylinder part 31.

[0063] The accommodation diameter di is the inner diameter of the outer cylinder portion 31, i.e., the inner diameter of the accommodation portion 34. The suction diameter dm is the inner diameter of the inner cylinder portion 32. The suction diameter dm is smaller than the accommodation diameter di. From the viewpoint of facilitating the formation of the outer cylinder portion 31 and the inner cylinder portion 32, each of the accommodation diameter di and the suction diameter dm is preferably 20 μm or more.

[0064] In the first state, the inner diameter of the needle-shaped portion 30 changes from the storage diameter di to the suction diameter dm. In other words, in the first state, the inner diameter of the needle-shaped portion 30 becomes smaller on the way from the tip to the base end. The outer diameter do of the implant 10 described above is equal to or larger than the suction diameter dm and is equal to or smaller than 2.5 times the storage diameter di.

[0065] When the inner diameter of the outer tube portion 31 is not constant, the accommodation diameter di is the inner diameter of the accommodation portion 34 at the tip of the accommodation portion 34. When the inner diameter of the inner tube portion 32 is not constant, the suction diameter dm is the inner diameter of the inner tube portion 32 at the tip of the inner tube portion 32. When the inner diameter of the inner tube portion 32 is constant, the suction diameter dm is the minimum value of the inner diameter of the needle-like portion 30. From the viewpoint of smooth formation and assembly of the outer tube portion 31 and the inner tube portion 32, it is preferable that the inner diameters of the outer tube portion 31 and the inner tube portion 32 are each constant, and that the accommodation portion 34 and the inner tube portion 32 are cylindrical.

[0066] [Graft uptake] A method for incorporating the transplant 10 into the cell transplantation device 20 will be described with reference to FIGS. 6, first, the needle-shaped portion 30 is put into a second state in which the tip of the inner cylinder portion 32 protrudes from the opening 33 at the tip of the outer cylinder portion 31. Then, the tip of the needle-shaped portion 30 in the second state, i.e., the tip of the inner cylinder portion 32, is brought close to the transplant 10 placed in a tray such as a culture vessel.

[0067] 7, when the inside of the inner cylindrical portion 32 is sucked by driving the suction portion 50, the implant 10 is attracted to the inner cylindrical portion 32 and is held at the tip of the inner cylindrical portion 32 so as to abut against the tip of the inner cylindrical portion 32. The outer diameter do of the implant 10 is larger than the suction diameter dm to such an extent that the implant 10 does not enter the inside of the inner cylindrical portion 32. If the outer diameter do of the implant 10 is 2.8 times or more the suction diameter dm, the implant 10 can be appropriately prevented from entering the inside of the inner cylindrical portion 32.

[0068] 8, with the implant 10 held at the tip of the inner cylinder part 32, the position changing part 60 is actuated, whereby the inner cylinder part 32 is moved relative to the outer cylinder part 31. As a result, the tip of the inner cylinder part 32 and the implant 10 are drawn into the inside of the outer cylinder part 31 from the opening 33, the needle-shaped part 30 enters the first state, and the implant 10 is housed in the housing part 34. This completes the uptake of the implant 10 into the needle-shaped part 30.

[0069] Here, the suction pressure P in the inner tubular portion 32 by the suction part 50 is set to a value that prevents the transplant 10 from being drawn into the inner tubular portion 32 by suction, depending on the outer diameter do of the transplant 10 relative to the suction diameter dm. If the outer diameter do of the transplant 10 is 5.1 times or more the suction diameter dm, the transplant 10 can be prevented from entering the inside of the inner tubular portion 32 even when the suction pressure P is as strong as -100 kPa.

[0070] In this embodiment, the suction pressure P is -100 kPa or more and -0.1 kPa or less. That is, when the strongest suction force is used, the suction pressure P is -100 kPa, and when the weakest suction force is used, the suction pressure P is -0.1 kPa. The suction pressure P is the maximum value of the suction pressure from the start to the end of suction.

[0071] If the suction pressure P is -0.1 kPa or stronger, the transplant 10 can be sucked and held at the tip of the inner tube 32. On the other hand, if the suction pressure P is too strong, the transplant 10 is deformed so that the part of the transplant 10 facing the opening at the tip of the inner tube 32 sinks into the opening, and such deformation may remain on the transplant 10 as a suction mark even after the suction is stopped. The remaining suction mark means that strong stress remains in the transplant 10, and such stress may cause mutation of the cell group 11, such as cell death. If the suction pressure P is -100 kPa or weaker, the formation of a suction mark on the transplant 10 is suppressed. In order to more suitably suppress the formation of a suction mark, the suction pressure P is preferably -80 kPa or more.

[0072] If the protective portion 12 is a gel made of an extracellular matrix, when the transplant 10 is sucked onto the tip of the inner tube portion 32 by suction within the range of the above-mentioned suction pressure P, a protective function for the cell group 11 is obtained to the extent that the transplant 10 is prevented from collapsing.

[0073] In particular, if the jelly strength I of the protective part 12 is 100 g or more, the transplant 10 is appropriately prevented from collapsing when the transplant 10 is adsorbed to the inner tube part 32 within the range of the above-mentioned suction pressure P. In other words, if the suction pressure P (kPa) and the jelly strength I (g) are set so that the suction pressure P and the jelly strength I of the protective part 12 satisfy the following formula (1), the transplant 10 is appropriately prevented from collapsing due to the holding of the transplant 10 by the inner tube part 32 using suction. -1.0≦P / I (1)

[0074] Since the transplant 10 has flexibility, even if the outer diameter do of the transplant 10 is larger than the storage diameter di, the transplant 10 can be taken into the storage section 34 through the opening 33 as long as the outer diameter do is 2.5 times or less than the storage diameter di. If the outer diameter do of the transplant 10 is larger than the storage diameter di, the transplant 10 rubs against the inner surface of the outer tube 31 when the transplant 10 is stored in the storage section 34 and when the transplant 10 is taken out of the storage section 34 in the living body. However, since the cell group 11 is covered by the protective section 12, the transplant 10 can be prevented from collapsing due to the above-mentioned rubbing. If the jelly strength I of the protective section 12 is 100 g or more, the transplant 10 can be more appropriately prevented from collapsing due to the above-mentioned rubbing.

[0075] The larger the outer diameter do of the transplant 10, the more the number of cells contained in the cell group 11 can be increased, and the greater the number of cells, the easier it is for the cell group 11 to grow and take root after transplantation. In addition, the larger the outer diameter do of the transplant 10, the thicker the protective part 12 can be made to enhance the protective function. On the other hand, the smaller the outer diameter of the needle-shaped part 30, the easier it is for the needle-shaped part 30 to pierce the living body, and the smaller the burden on the living body when the needle-shaped part 30 advances. Since the smaller the storage diameter di, the smaller the outer diameter of the needle-shaped part 30, i.e., the outer diameter of the outer tube part 31, can be made smaller, from the viewpoint of improving the ease with which the needle-shaped part 30 can pierce the living body and reducing the burden on the living body, it is preferable that the storage diameter di is smaller.

[0076] If the outer diameter do of the graft 10 is greater than 1.0 times and not more than 2.5 times the storage diameter di, it is possible to transplant a graft 10 with a large outer diameter do while suppressing the storage diameter di from increasing, as compared to when the outer diameter do is smaller than the storage diameter di. Therefore, it is possible to simultaneously promote the growth and engraftment of the cell group 11, improve the ease with which the needle-shaped portion 30 can be inserted into the body, and reduce the burden on the body. When the needle-shaped portion 30 is inserted into the skin, it is preferable that the outer diameter of the outer tube portion 31 is 600 μm or less, from the viewpoint of improving the ease with which the needle-shaped portion 30 can be inserted into the body and reducing the burden on the body.

[0077] When the outer diameter do of the transplant 10 is larger than the storage diameter di, in order to draw the transplant 10 into the storage section 34 while keeping the transplant 10 held at the tip of the inner tube section 32, it is preferable to increase the suction pressure P as the outer diameter do of the transplant 10 increases relative to the storage diameter di.

[0078] On the other hand, if the outer diameter do of the transplant 10 is smaller than the storage diameter di, friction of the transplant 10 against the inner surface of the outer tube 31 during storage or release of the transplant 10 is suppressed, thereby reducing the load on the transplant 10.

[0079] A protective liquid, which is a liquid for protecting the transplant 10, may be introduced into the needle-shaped portion 30 together with the transplant 10 from a tray such as a culture vessel. The protective liquid includes, for example, physiological saline and nutrients.

[0080] [Placement of implants in the body] A method for placing the implant 10 in a living body will be described with reference to FIGS. Once the transplant plant 10 has been taken into the needle-shaped portion 30, the cell transplantation device 20 is transported to the transplantation site Sk, which is, for example, the skin of the head, of a living body, with the transplant plant 10 contained in the container portion 34, i.e., with the needle-shaped portion 30 maintained in the first state.

[0081] 9, the transplant site Sk is pierced by the needle-shaped portion 30. At this time, the tip of the outer tube portion 31 is located at the tip of the cell transplantation device 20. Since the tip of the outer tube portion 31 has a shape that allows it to easily pierce a living body, the needle-shaped portion 30 can smoothly enter the transplant site Sk. Note that the needle-shaped portion 30 may enter the transplant site Sk in a direction perpendicular to the surface of the transplant site Sk, or in a direction inclined to the surface of the transplant site Sk.

[0082] When the tip of the outer cylinder part 31 advances to the target area for transplantation, the position changing part 60 is actuated to move the inner cylinder part 32 relative to the outer cylinder part 31, and the needle-shaped part 30 is put into the second state, as shown in Fig. 10. As a result, the transplant 10 comes out from the opening 33 of the outer cylinder part 31 together with the tip of the inner cylinder part 32. Then, the suction by the suction part 50 is stopped, so that the hold of the transplant 10 by the inner cylinder part 32 is released, and the transplant 10 is placed in the target area for transplantation.

[0083] When the needle-shaped portion 30 is in the second state, the outer cylinder portion 31 may be retracted in a direction in which the needle-shaped portion 30 is removed from the transplantation site Sk, or the inner cylinder portion 32 may be advanced into the transplantation site Sk without changing the position of the outer cylinder portion 31. From the viewpoint of reducing the load on the transplant 10, it is preferable that the outer cylinder portion 31 is retracted, and the tip portion of the inner cylinder portion 32 and the transplant 10 are placed in the space inside the transplantation site Sk where the tip portion of the outer cylinder portion 31 was located. This prevents the transplant 10 from being pressed by the surrounding tissues when the transplant 10 comes out of the outer cylinder portion 31. Note that since the cell group 11 is covered by the protective portion 12, even if a load is applied to the transplant 10 when the transplant 10 is placed in the living body, the effect on the cell group 11 is kept small.

[0084] If a protective liquid has been taken into the needle-shaped part 30 together with the transplant 10, the protective liquid may also be discharged to the target area of ​​transplantation. The suction part 50 may be configured to be capable of applying pressure in addition to suction to the inner tube part 32, and air may be sent into the inner tube part 32 when the transplant 10 is released from its hold.

[0085] 11, when the transplant 10 is placed in the target area for transplantation, the inner cylinder part 32 is moved and drawn into the outer cylinder part 31, and the needle-shaped part 30 is pulled out from the transplant site Sk. This completes the placement of the transplant 10 in the living body. Note that after the transplant 10 is placed, the inner cylinder part 32 may not be moved, and the needle-shaped part 30 may be pulled out while the transplant 10 is still in the second state.

[0086] [Variations] The needle-shaped portion 30 is not limited to a configuration including an outer cylindrical portion 31 and an inner cylindrical portion 32, but may have a configuration in which the inner diameter of the needle-shaped portion 30 becomes smaller from the tip to the base end of the needle-shaped portion 30 when the implant 10 is housed therein. For example, as shown in Fig. 12, the needle-shaped portion 30 may be a single cylindrical structure whose inner diameter changes midway.

[0087] 12, the needle-shaped portion 30 is composed of a cylindrical portion 35 having a multi-stage cylindrical shape. The cylindrical portion 35 has a storage portion 34 that communicates with an opening 33 at the tip end, and a small diameter portion 36 that has an inner diameter smaller than the inner diameter of the storage portion 34. The small diameter portion 36 is located on the side of the storage portion 34 where the base end of the cylindrical portion 35 is located. The storage diameter di is the inner diameter of the storage portion 34, and the suction diameter dm is the inner diameter of the small diameter portion 36. When the inside of the tubular portion 35 is suctioned by the suction portion 50 , the implant 10 is drawn into the inside of the tubular portion 35 through the opening 33 and is contained in the container portion 34 .

[0088] Figure 12 illustrates an example in which the inner diameter of the needle-shaped portion 30 switches from the storage diameter di to the suction diameter dm at a specific position, forming a step inside the needle-shaped portion 30, but the inner diameter of the needle-shaped portion 30 may change gradually.

[0089] If the outer diameter do of the transplant 10 is equal to or greater than the minimum inner diameter of the needle-shaped portion 30, when the transplant 10 is housed inside the needle-shaped portion 30, the transplant 10 will come into contact with the needle-shaped portion 30 at least near the portion where the inner diameter is minimum. Therefore, the transplant 10 will be subjected to an external force due to contact with the needle-shaped portion 30, but since the cell group 11 is covered with the protective portion 12, the cell group 11 can be protected from the external force.

[0090] If the suction pressure P by the suction part 50 is -100 kPa or more and -0.1 kPa or less, and the outer diameter do of the transplant 10 is 2.5 times or less the storage diameter di, the transplant 10 can be taken into the needle-shaped part 30 while preventing the transplant 10 from collapsing.

[0091] In a configuration in which the needle-shaped portion 30 includes an outer tube portion 31 and an inner tube portion 32, the inner tube portion 32 may not be moved relative to the outer tube portion 31 and may always be located inside the outer tube portion 31. In this case, the inside of the inner tube portion 32 is sucked by the suction portion 50, so that the transplant 10 is drawn into the inside of the outer tube portion 31 from the opening 33 and is contained in the containing portion 34.

[0092] Furthermore, the cell transplantation kit may include the protective part 12 in a material state, and the step of preparing the transplant 10 in which the cell group 11 is covered with the protective part 12 based on the formation of the protective part 12 may be performed by the user of the cell transplantation kit. In short, the cell transplantation kit includes the transplant 10 in a state in which at least a part of the cell group 11 is covered with the protective part 12 together with the cell transplantation device 20, and the jelly strength of this protective part 12 may be 100 g or more, or the cell transplantation kit may include the material of the protective part 12 together with the cell transplantation device 20 so that the protective part 12 having a jelly strength of 100 g or more can be formed around the cell group 11.

[0093] Furthermore, the cell transplantation kit may include a tray for holding the transplant 10, in addition to the transplant 10 and the cell transplantation device 20. The tray may be a culture vessel used for culturing the cell group 11, or may be a vessel different from the culture vessel, and the cell group 11 may be transferred from the culture vessel to the tray. Furthermore, the transplant 10 may be produced in the tray, or the transplant 10 produced in another vessel may be transferred to the tray.

[0094] The tray preferably has a holding area for the transplant 10, for example a recess, and one holding area holds one transplant 10. This allows the transplant 10 to be efficiently taken into the needle-shaped part 30 by aligning the needle-shaped part 30 of the cell transplantation device 20 with the holding area of ​​the tray.

[0095] The cell transplantation device 20 may include a plurality of needle-shaped portions 30. If the cell transplantation device 20 includes a plurality of needle-shaped portions 30, it is possible to transplant a plurality of transplants 10 together. In this case, suction by the suction unit 50 may be performed on the plurality of needle-shaped portions 30 all at once, or may be performed independently for each needle-shaped portion 30, and it is sufficient that the suction pressure P in each needle-shaped portion 30 is −100 kPa or more and −0.1 kPa or less.

[0096] Furthermore, the cell group 11 contained in the transplant 10 does not have to be a cell group that contributes to hair growth or hair development, but may be a cell group that exerts a desired effect by being placed in the tissue of a living body. For example, the cell group 11 may be a cell group that exerts an effect for cosmetic purposes, such as eliminating wrinkles in the skin or improving the moisturizing state.

[0097] [Example] The above-mentioned cell transplantation kit and method for incorporating the transplant will be described using specific examples and comparative examples.

[0098] (Example) <Transplant> A cell suspension containing human dermal papilla cells (C-12071, manufactured by PromoCell) and a collagen solution (Cellmatrix Type IA, manufactured by Nitta Gelatin) with a concentration of 2.4 mg / ml was supplied to each well of a round-bottom 96-well plate, and the collagen was allowed to harden by standing at 37°C for 5 minutes. Then, human dermal papilla cell growth medium (C-26501, manufactured by PromoCell) was added, and the cells were cultured in the well for 3 days at 37°C and a CO2 concentration of 5%, forming a cell mass inside the collagen. This resulted in a transplant in which the cell mass, a group of cells, was covered with a protective part made of collagen.

[0099] By changing the amount of cell suspension supplied to the well, the outer diameter of the formed implant can be changed. In addition, by adjusting the ratio of cells to collagen solution in the cell suspension, the outer diameter of the cell group and the thickness of the protective part can be adjusted. Specifically, the number of cells supplied to each well was 5 × 10 when evaluating the suction pressure described below. 3 The outer diameter of the implant was evaluated using 5 × 10 cells. 3 cells~20×10 3 There are 63 possible combinations between cells.

[0100] 13 to 15 show cross-sectional images of the transplant obtained by performing Masson's trichrome staining on a section prepared from the transplant formed to have a protective portion. In FIG. 13, the entire aggregated cell group 11 is covered with the protective portion 12. In FIG. 14, a part of the aggregated cell group 11 is covered with the protective portion 12. In FIG. 15, the cells constituting the cell group 11 are dispersed in the protective portion 12.

[0101] Whether or not the cell group forms a clump-like aggregate in the transplant can be adjusted by, for example, adjusting the balance between the number of cells and the amount of the protective part while taking into account the migration and aggregation properties of the cells. Specifically, cells of a type that have a low tendency to migrate tend to disperse in the protective part, and cells of a type that tend to aggregate tend to form cell clumps in the protective part. If the number of cells is small relative to the amount of the protective part, the interaction between the cells is weak and the cells are less likely to gather, making it easier to form a transplant in which the cells are dispersed in the protective part.

[0102] <Cell transplant device> A cell transplantation device having a needle-shaped portion including an outer cylinder portion and an inner cylinder portion was prepared. The outer cylinder portion is a 25G injection needle. That is, the container portion of the outer cylinder portion is cylindrical, and its inner diameter is constant at 400 μm. The outer cylinder portion is made of stainless steel (SUS304). The inner cylinder portion is cylindrical, and the end face of the tip portion of the inner cylinder portion is a plane perpendicular to the extending direction of the inner cylinder portion. The outer diameter of the inner cylinder portion is constant at 360 μm, and the inner diameter of the inner cylinder portion is constant at 170 μm. The inner cylinder portion is made of stainless steel (SUS304). The inner cylinder portion is configured to be movable relative to the outer cylinder portion, and a suction portion including a pump mechanism is connected to the base end of the inner cylinder portion.

[0103] Thus, the storage diameter di in the cell transplantation device of the embodiment is 400 μm, the suction diameter dm is 170 μm, and the suction diameter dm is the minimum value of the inner diameter of the needle-shaped part. Also, as described above, the cross-sectional shape of the outer cylinder is a circle with an inner diameter of 400 μm, and the arithmetic mean roughness Ra of the inner surface of the outer cylinder is 400 nm. The moving speed of the inner cylinder relative to the outer cylinder is set to 1.5 mm / s.

[0104] (Comparative Example) <Transplant> In a round-bottom 96-well plate, 5 × 10 human dermal papilla cells (C-12071, PromoCell) were placed in each well. 3 The human dermal papilla cells and a dermal papilla cell growth medium (C-26501, manufactured by PromoCell) were supplied, and the human dermal papilla cells were cultured for three days in an environment of 37°C and a CO2 concentration of 5%. This resulted in the formation of cell clusters. The comparative example of the transplant consisted only of cell clusters, which were not covered with a protective part.

[0105] <Cell transplant device> As the cell transplantation device of the comparative example, a device having the same configuration as the cell transplantation device of the example was used.

[0106] (Transplantation Operation Test) The implants of the examples and comparative examples were tested to confirm the presence or absence of deformation of the implants due to the procedure for implantation as follows. In the examples, the outer diameter of the implant is about 600 μm, and the jelly strength of the protective part of the implant is about 150 g. In the comparative examples, the outer diameter of the implant is about 600 μm.

[0107] First, the inside of the inner tube of the needle-shaped part in the second state of the cell transplantation device was suctioned with a suction pressure of -5 kPa, and the transplant was held at the tip of the inner tube. The inner tube and the transplant were then drawn into the outer tube to set the needle-shaped part to the first state, and the transplant was taken into the needle-shaped part. Thereafter, the needle-shaped part was again set to the second state and suction was stopped, releasing the transplant from the needle-shaped part into the petri dish. The released transplant was observed using an inverted microscope.

[0108] Figure 16 shows an image of the implant of the Example after release, and Figure 17 shows an image of the implant of the Comparative Example after release. As Figures 16 and 17 show, no collapse was observed in the implant of the Example having a protective part, whereas the implant of the Comparative Example not having a protective part collapsed so that the implant was divided. This confirmed that the cell population can be protected by covering the cell population with a protective part.

[0109] (Suction pressure evaluation) The suction pressure of the implant of the embodiment was changed to observe whether the implant collapsed as follows. The outer diameter of the implant was about 580 μm, and the jelly strength of the protective part of the implant was about 150 g. The suction pressure was set to each of -19 kPa, -32 kPa, -52 kPa, and -71 kPa, and the following test was performed for each suction pressure.

[0110] The inside of the inner tube of the needle-shaped part in the second state of the cell transplantation device was suctioned with a set suction pressure, the transplant was held at the tip of the inner tube, and then the inner tube and the transplant were pulled into the outer tube to set the needle-shaped part to the first state, and the transplant was taken into the needle-shaped part. Five seconds after the transplant was taken into the needle-shaped part, the needle-shaped part was again set to the second state and suction was stopped, releasing the transplant from the needle-shaped part into the petri dish. The released transplant was observed using an inverted microscope.

[0111] Observation of the released implant did not reveal any collapse of the implant at any of the suction pressures, confirming that the implant can be taken up and released into the needle-shaped portion without collapsing within the above-mentioned suction pressure range.

[0112] In addition, in all cases of suction pressure, the graft was held at the tip of the inner tube, the graft did not enter the inside of the inner tube, and no suction marks were observed on the graft. In addition, when the same test as above was performed using the graft of the embodiment having an outer diameter of about 900 μm and the suction pressure was set to -100 kPa, no entry of the graft into the inner tube or no formation of suction marks was observed, and no collapse of the graft was observed.

[0113] (Evaluation of the outer diameter of the implant) The outer diameter of the implant of the Example was changed, and the following observations were made as to whether the implant could be taken up by the needle-shaped portion and whether the implant was destroyed.

[0114] First, 63 implants with different outer diameters were prepared. In these implants, the minimum outer diameter was 486 μm, and the maximum outer diameter was 1378 μm. The jelly strength of the protective part in each implant was about 150 g. The following tests were performed on each implant.

[0115] The inner tube of the needle-shaped part in the second state of the cell transplantation device was suctioned with a suction pressure of -50 kPa, and the transplant was held at the tip of the inner tube.The inner tube and the transplant were then pulled into the outer tube to return the needle-shaped part to the first state, and it was confirmed whether the transplant had been taken up into the needle-shaped part.

[0116] When the graft was taken up into the needle-shaped part, the needle-shaped part was again set to the second state and suction was stopped, whereby the graft was released from the needle-shaped part into the petri dish. The released graft was observed using an inverted microscope.

[0117] For nine transplants with an outer diameter of 1086 μm or more, the transplants were blocked at the opening of the outer tube, and the transplants could not be taken into the needle-shaped part. For 54 transplants with an outer diameter of 978 μm or less, it was possible to take them into the needle-shaped part. For these transplants, no collapse of the transplants was confirmed after observation after release. Therefore, it was confirmed that if the outer diameter of the transplant is 2.5 times or less than the storage diameter, it is possible to take the transplant into and release it from the needle-shaped part without causing collapse of the transplant.

[0118] As described above in the embodiments and examples, the cell transplantation kit, the cell transplantation device, and the method for incorporating a transplant can provide the following effects. (1) Since the cell group 11 is covered with the gel-like protective portion 12, it is possible to protect the cell group 11 from external forces that the transplant 10 receives due to contact between the cell transplant device 20 and the transplant 10, and mutations such as collapse of the cell group 11 can be prevented.

[0119] (2) When the implant 10 is taken into the needle-shaped portion 30, the suction pressure P for attracting the implant 10 to the needle-shaped portion 30 is −100 kPa or more and −0.1 kPa or less. This allows the implant 10 to be attracted to the needle-shaped portion 30 by suction while suppressing deformation of the implant 10, and the implant 10 can be taken into the needle-shaped portion 30.

[0120] (3) If the jelly strength of the protective part 12 is 100 g or more, the cell group 11 can be adequately protected. In particular, the transplant 10 can be adequately prevented from collapsing when the transplant 10 is adsorbed to the inner tube part 32 within the range of the suction pressure P. In addition, the transplant 10 can be adequately prevented from collapsing due to friction of the transplant 10 against the inner surface of the outer tube part 31.

[0121] (4) The protective part 12 contains an extracellular matrix, which provides a suitable function for protecting the cell group 11 and improves the suitability of the transplant 10 for placement in a living body. For example, by using an extracellular matrix having a function of assisting adhesion between cells as the protective part 12, it is possible to promote the survival of the transplant 10. Furthermore, since collagen is an extracellular matrix that is particularly abundant in the skin, if the protective part 12 contains collagen, the biocompatibility of the protective part 12 is suitably improved when the transplant 10 is transplanted into the skin.

[0122] (5) Since the outer diameter do of the transplant 10 is 2.5 times or less the storage diameter di of the storage section 34, the transplant 10 can be smoothly stored in the storage section 34. In addition, since the transplant 10 having an outer diameter do larger than the storage diameter di can be taken into the needle-shaped section 30, the transplant 10 having a large outer diameter do can be transplanted while suppressing the expansion of the outer diameter of the needle-shaped section 30. Therefore, it is possible to improve the ease with which the needle-shaped section 30 can be inserted into the living body, reduce the burden on the living body, and promote the growth and engraftment of the cell group 11.

[0123] (6) Since the outer diameter do of the transplant 10 is 2.8 times or more the suction diameter dm of the needle-shaped portion 30, the transplant 10 is retained midway within the needle-shaped portion 30. Specifically, when the needle-shaped portion 30 has an outer tubular portion 31 and an inner tubular portion 32, the transplant 10 is prevented from entering the inner tubular portion 32, and the transplant 10 is retained at the tip of the inner tubular portion 32. Therefore, the uptake and release of the transplant 10 into the needle-shaped portion 30 proceeds smoothly.

[0124] (7) The needle-shaped portion 30 has an outer tube portion 31 and an inner tube portion 32, and the inner tube portion 32 is configured to be movable relative to the outer tube portion 31 along the extending direction of the needle-shaped portion 30. Then, with the tip portion of the inner tube portion 32 protruding from the opening 33 of the outer tube portion 31, the suction portion 50 sucks inside the inner tube portion 32, thereby holding the transplant 10 at the tip portion of the inner tube portion 32. Therefore, the transplant 10 to be taken in can be accurately captured and taken in the needle-shaped portion 30.

[0125] (8) The cell group 11 includes a hair follicle primordium. A hair follicle primordium has a structure in which an aggregated portion of mesenchymal cells and an aggregated portion of epithelial cells are adjacent to each other, and therefore often has a shape other than a substantially spherical shape. Therefore, since a locally weak portion is likely to be formed in the cell group 11, the cell group 11 is likely to collapse due to an external force if the protective part 12 is not present. In addition, if either the aggregated portion of mesenchymal cells or the aggregated portion of epithelial cells is destroyed, the function as an primordium is lost, and therefore the collapse of the cell group 11 has a greater impact on the function of the cell group 11 than a cell group 11 in which the same type of cells are gathered. Therefore, the effect of protecting the transplant 10 by the protective part 12 is highly obtained.

[0126] (9) In the method of taking in the transplant 10, the transplant 10 is attracted to the needle-shaped part 30 by suction with the suction part 50 so that the suction pressure P (kPa) generated by the suction part 50 and the jelly strength I (g) of the protective part 12 satisfy -1.0≦P / I, and the transplant 10 is taken inside through the opening 33 at the tip of the needle-shaped part 30. This effectively prevents the transplant 10 from collapsing due to the intake of the transplant 10 using suction.

[0127] [Note] The means for solving the above problems include the following supplementary notes as technical ideas derived from the above embodiments.

[0128] A cell transplantation kit comprising: a material capable of forming a gel-like protective part that covers at least a portion of a cell group; and a cell transplantation device for placing a transplant including the cell group and the protective part in a living body, The cell transplantation device comprises: The needle-shaped portion extends in a cylindrical shape, and a suction portion suctions the inside of the needle-shaped portion. the needle-shaped portion is configured to attract the implant by suction with the suction portion and to be able to take in the implant from an opening at the tip end of the needle-shaped portion, and when the implant is taken in, the inner diameter of the needle-shaped portion becomes smaller on the way from the tip end to the base end of the needle-shaped portion, The suction pressure generated by the suction unit is -100 kPa or more and -0.1 kPa or less, The outer diameter of the implant is equal to or greater than the minimum inner diameter of the needle-shaped portion; The jelly strength of the protective part is 100g or more. Cell transplant kit.

[0129] According to the above configuration, since a transplant in which the cell group is covered with the protective part can be formed, it is possible to protect the cell group from external forces that the transplant receives due to contact between the cell transplant device and the transplant, and to prevent the cell group from being deformed, etc. Furthermore, if the suction pressure is within the above range, the transplant can be attracted to the needle-shaped part by suction while preventing deformation of the transplant, and the transplant can be taken into the needle-shaped part. [Explanation of symbols]

[0130] 10...Implant 11...Cell group 12...Protection part 20...Cell transplantation device 30...Needle-shaped part 31…Outer cylinder part 32…Inner cylinder 33…Aperture 34…Storage section 50…Suction part

Claims

1. A cell transplantation kit comprising a transplant containing a cell group and a cell transplantation device for placing the transplant in a living body, The cell transplantation device comprises: The needle-shaped portion has an outer cylindrical portion extending in a cylindrical shape and an inner cylindrical portion extending in a cylindrical shape inside the outer cylindrical portion, and a suction portion that sucks the inside of the inner cylindrical portion, the inner cylinder portion is configured to be movable relative to the outer cylinder portion between a first position where a tip portion of the inner cylinder portion is located inside the outer cylinder portion and a second position where the tip portion of the inner cylinder portion protrudes from an opening at the tip portion of the outer cylinder portion, The needle-shaped portion attracts the transplant together with a liquid for protecting the transplant by suction with the suction portion, holds the transplant outside the tip of the inner cylindrical portion so as to abut against the tip of the inner cylindrical portion, and is configured so that the inner cylindrical portion can be set at the first position and the transplant can be taken inside through the opening of the outer cylindrical portion, which is the opening at the tip of the needle-shaped portion, and when the transplant has been taken in, the inner diameter of the needle-shaped portion becomes smaller on the way from the tip to the base end of the needle-shaped portion, The outer cylinder portion has a receiving portion communicating with the opening of the outer cylinder portion, the receiving portion receiving the implant that has been taken in, The suction pressure generated by the suction unit is −100 kPa or more and −0.1 kPa or less, The implant includes a gel-like protective portion that covers at least a portion of the cell group, The outer diameter of the implant is larger than the inner diameter of the tip of the inner cylinder portion and is greater than 1.0 times and less than 2.5 times the inner diameter of the container portion; The jelly strength of the protective part is 100 g or more. Cell transplant kit.

2. The outer diameter of the implant is 2.8 times or more the inner diameter of the distal end of the inner cylinder. The cell transplant kit according to claim 1 .

3. The protective portion includes an extracellular matrix. The cell transplantation kit according to claim 1 or 2.

4. The protective portion includes collagen. The cell transplant kit according to any one of claims 1 to 3.

5. The cell population comprises a hair follicle primordium. The cell transplantation kit according to any one of claims 1 to 4.

6. A cell transplantation device for placing a transplant in a living body, the transplantation including a cell group and a gel-like protective part that covers at least a part of the cell group, The cell transplantation device comprises: A needle-shaped portion having an outer cylindrical portion extending in a cylindrical shape and an inner cylindrical portion extending in a cylindrical shape inside the outer cylindrical portion; A suction portion that sucks the inside of the inner cylindrical portion, the inner cylinder portion is configured to be movable relative to the outer cylinder portion between a position where a tip portion of the inner cylinder portion is located inside the outer cylinder portion and a position where the tip portion of the inner cylinder portion protrudes from an opening at the tip portion of the outer cylinder portion, the needle-shaped portion is configured to attract the transplant together with a liquid for protecting the transplant by suction with the suction portion, hold the transplant outside the tip portion of the inner cylindrical portion so as to abut against the tip portion, and take the transplant into the needle-shaped portion through the opening of the outer cylindrical portion; The outer cylinder portion has a receiving portion communicating with the opening of the outer cylinder portion, the receiving portion receiving the implant that has been taken in, The inner diameter of the tip of the inner cylindrical portion and the inner diameter of the container portion are each such that the outer diameter of the implant is larger than the inner diameter of the tip of the inner cylindrical portion and is greater than 1.0 times and less than 2.5 times the inner diameter of the container portion; The suction pressure generated by the suction part is -100 kPa or more and -0.1 kPa or less. Cell transplant device.

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