JP2020010620A - Housing device of cells for transplantation and housing system of cells for transplantation - Google Patents

Abstract

To provide a housing device of cells for transplantation and a housing system of cells for transplantation which can suppress deflection of an oxygen permeable membrane or an immunity isolating membrane covering a cell chamber, inside a biological body.SOLUTION: A housing device of cells for transplantation comprises: an enclosure 11; a hollow part 13 which is formed inside the enclosure 11; an introduction flow path 14 which is connected to the hollow part 13 and introduces oxygen from outside into the hollow part 13; a discharge flow path 15 which is connected to the hollow part 13 and discharges gas inside the hollow part 13; a cell chamber 17 which is formed inside the enclosure 11 and in which a cell is housed; an oxygen permeable membrane 16 which is provided for the enclosure 11 so as to partition the hollow part 13 and the cell chamber 17; an immunity isolating membrane 18 which is provided for the enclosure 11 so as to close an outer side of the cell chamber 17; and a deflection suppressing member 19 which suppresses deflection of a membrane which can be a lower side of the cell chamber 17 out of the oxygen permeable membrane 16 and the immunity isolating membrane 18, and the device is transplanted into a biological body.SELECTED DRAWING: Figure 5

Description

  The present invention relates to a transplant cell storage device and a transplant cell storage system.

  As a background art of this technical field, there is Japanese Patent Application Laid-Open No. 11-506696 (Patent Document 1). This publication states that "Surface microfabrication and bulk microfabrication are employed to realize a porous membrane having a bulk substrate to form a particle filter. Filters have been studied enough to facilitate handling. The filter can be used as a diffusion barrier under high pressure.The disclosed etching fabrication method is simple, reliable, compatible with integrated circuits, and thus amenable to mass production.Fluid properties, encapsulation, or filter Electronic circuits may be integrated on the surface of the filter, if desired, for some purposes, such as automatic cleaning or charging of the surface of the filter (see summary).

Japanese Patent Publication No. 11-506696

Patent Document 1 describes a microfabricated porous film that is a silicon plate. It is conceivable that this silicon plate is used as a membrane for covering a cell room for accommodating cells of the cell accommodating device for transplantation. However, since the plate made of silicon is hard and heavy, we do not want to put it in the living body as much as possible.
Therefore, it is desirable to form the casing, the immune isolation membrane, the oxygen permeable membrane, and the like of the cell storage device for transplantation using a lightweight material having some flexibility (flexibility).

However, if an immunoisolation membrane or an oxygen permeable membrane that covers the cell chamber for accommodating the cells is formed of a flexible material, the cells in the cell chamber are bent in the living body when implanted in the living body, and the cells in the cell chamber are biased to a part of the cell chamber. As a result, there is a problem that the function and viability of the cell are reduced.
Therefore, an object of the present invention is to provide a cell storage device for transplantation and a cell storage system for transplantation that can suppress the in vivo deformation of an oxygen permeable membrane or an immunoisolation membrane covering a cell chamber.

  In order to solve the above problems, a cell storage device for transplantation, which is one embodiment of the present invention, includes a housing, a cavity formed inside the housing, and a cavity connected to the cavity from the outside and into the cavity. An introduction flow path for introducing oxygen, a discharge flow path connected to the cavity and discharging gas in the cavity, a cell chamber formed inside the housing and containing cells, the cavity and the cells An oxygen permeable membrane provided in the housing so as to partition the cell compartment, an immunoisolation membrane provided in the housing so as to close the outside of the cell chamber, the oxygen permeable membrane and the immunoisolation A bending suppression member for suppressing bending of the membrane that may be below the cell chamber of the membrane, and is implanted in a living body.

Advantageous Effects of Invention According to the present invention, it is possible to provide a transplant cell storage device and a transplant cell storage system that can suppress the in-vivo deformation of an oxygen-permeable membrane or an immune isolation membrane that covers a cell chamber.
Problems, configurations, and effects other than those described above will be apparent from the following description of the embodiments.

It is a longitudinal section of the cell storage device for transplants concerning Embodiment 1 of the present invention. FIG. 2 is an enlarged vertical cross-sectional view of the oxygen permeable membrane or the immunoisolation membrane showing an example in which a deflection suppressing member is embedded in the oxygen permeable membrane or the immunoisolation membrane of the cell storage device for transplantation according to the first embodiment of the present invention. FIG. 2 is an enlarged longitudinal sectional view of a case where a membrane-shaped deflection suppressing member is formed from below on an oxygen permeable membrane or an immunoisolation membrane of the cell storage device for transplantation according to the first embodiment of the present invention. 1 is a block diagram illustrating a schematic configuration of a transplant cell storage system including a transplant cell storage device according to a first embodiment of the present invention. It is a longitudinal cross-sectional view of the cell storage device for transplantation which concerns on Example 2 of this invention. It is a top view of the hollow part of the cell storage device for transplantation which concerns on Example 2 of this invention. It is a longitudinal section of the cell storage device for transplantation concerning Example 3 of the present invention. It is a longitudinal section of the cell storage device for transplantation concerning Example 4 of the present invention. It is a top view of the hollow part of the cell storage device for transplantation which concerns on Example 5 of this invention. It is a top view of the hollow part of the cell storage device for transplantation which concerns on Example 6 of this invention. It is an exploded perspective view of the cell storage device for transplantation concerning Example 7 of the present invention. FIG. 7 is a plan view of a cavity in a case where a deflection suppressing member as a comparative example of FIG. 6 is not provided.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  The cell-transplanting device for transplantation is a device in which predetermined cells are accommodated therein and transplanted into a living body of a human or an animal, and a medical effect is exerted by secretions secreted by the cells.

  To explain a typical example, cells of a pancreatic islet obtained by excision from a human body in a brain dead state or derived from iPS cells (induced Pluripotent Stem cells) are implanted into a human cell body in a cell storage device for transplantation. The example used in is mentioned. Thereby, type 1 diabetes can be treated with insulin secreted by the pancreatic islets.

As a technique related to such a cell storage device for transplantation, a technique disclosed in Patent Document 1 is known. That is, Patent Document 1 describes a microfabricated porous membrane that is a silicon plate. It is conceivable that this silicon plate is used as a membrane for covering a cell room for accommodating cells of the cell accommodating device for transplantation. However, since the plate made of silicon is hard and heavy, we do not want to put it in the living body as much as possible.
Therefore, it is desirable to form the casing, the immune isolation membrane, the oxygen permeable membrane, and the like of the cell storage device for transplantation using a lightweight material having some flexibility (flexibility).

However, if an immunoisolation membrane or an oxygen permeable membrane that covers the cell chamber for accommodating the cells is formed of a flexible material, the cells in the cell chamber are bent in the living body when implanted in the living body, and the cells in the cell chamber are biased to a part of the cell chamber. Cells may not get enough oxygen and nutrients. Therefore, there is a problem that the function and viability of the cell may be reduced.
Therefore, hereinafter, a transplant cell storage device and a transplant cell storage system that solves such a problem will be described.

  FIG. 1 is a longitudinal sectional view of the cell storage device 1 for transplantation according to the first embodiment. The cell storage device 1 for transplantation has a housing 11. The housing 11 may have a substantially rectangular outer shape as viewed from above, a substantially circular shape, or various shapes. In the example shown in FIG. 1, the outer shape of the vertical cross section of the housing 11 is rectangular, and a step portion 12 that forms a step with the housing 11 is provided in the lower central portion of the housing 11. Various materials can be used for the housing 11 and the stepped portion 12 as long as the material does not cause a serious problem on the health and living aspects of the patient even if it is left in the living body for a long time. However, considering the indwelling in a living body for a long period of time, a material that is too hard and a heavy material may be a burden on patients and the like, so that it has flexibility and flexibility to some extent, and Desirably, it is a lightweight material. Examples of such a material include a resin. In addition, as long as the housing 11 has sufficient strength, it is preferable that the volume be as small as possible from the viewpoint of burden on the patient or the like. From this point, it is desirable that the housing 11 has a flat shape. The housing 11 shown in FIG. 1 (similarly in a vertical cross-sectional view of the housing 11 in another embodiment described below) is drawn with a certain thickness in the vertical direction of the drawing for convenience. It is desirable that the actual product be in a flat and thin form at the top and bottom of the figure.

A cavity 13 is formed inside the housing 11. The casing 11 is a flow path connected to the cavity 13 by penetrating from the lower end of the step portion 12 to the cavity 13, and is provided with an introduction flow path 14 for introducing oxygen into the cavity 13 from the outside. ing. Similarly, the flow path is connected to the cavity 13 by penetrating the housing 11 from the lower end of the step portion 12 to the cavity 13. There is also provided a discharge flow path 15 for discharging the water.
In the housing 11, a cell room 17 which is a space adjacent to the cavity 13 with the oxygen permeable membrane 16 interposed therebetween is provided. The cell room 17 is a space in which a predetermined cell tissue such as the above-mentioned pancreatic islet cells is stored.

  The oxygen permeable membrane 16 is provided in the housing 11 so as to partition the cavity 13 from the cell chamber 17. The oxygen permeable film 16 is a film that does not allow moisture such as cells and body fluids to pass therethrough but allows oxygen to permeate. Thereby, oxygen is supplied to the cell chamber 17 through the oxygen permeable membrane 16, and carbon dioxide generated in the cell chamber 17 is discharged out of the cell chamber 17 through the oxygen permeable membrane 16. For such a purpose, it is desirable that the oxygen permeable membrane has a large surface area.

  As the oxygen permeable film 16, various materials can be used as long as the material has a relatively high oxygen permeability coefficient. For example, a film having physically fine holes can be used. For example, a thin film of a silicone material can be used. Further, ePTFE (expanded polytetrafluoroethylene) membrane and PTFE (polytetrafluoroethylene) non-woven fabric developed by W.L.

On the side opposite to the cavity 13 of the cell chamber 17, the upper side of the housing 11 in FIG. 1 is open to the outside, and the housing 11 is provided with an immunoisolation membrane 18 so as to close the opening. I have. The immunoisolation membrane 18 is a membrane that does not allow cells to pass therethrough but allows moisture such as body fluids to pass. This prevents the cells in the cell chamber 17 from being attacked by the immune cells of the living body, and prevents the cells in the cell chamber 17 from leaking out of the cell storage device 1 for transplantation. The immune isolation membrane 18 is capable of transmitting nutrients and the like in a body fluid of a living body and supplying the cells in the cell compartment 17, and is capable of transmitting metabolites and useful secretions of the cells and transmitting substances to tissues of the living body. It is also a membrane for creating a mobile environment. Therefore, it is desirable that the immunoisolation membrane 18 also has a large surface area.
Various materials can be used as the material of the immunoisolation film 18 as long as these materials can exhibit these functions. Examples of the material for the immunoisolation membrane 18 include porous polycarbonate.

  As described above, it is desirable that the housing 11 has a flat shape. When cells are introduced into the cell chamber 17 of such a flat casing 11, it can be realized by storing a cell suspension containing cells in the cell chamber 17. This cell suspension is poured in a state where a force is applied to a thin film such as the oxygen permeable membrane 16, that is, the oxygen permeable membrane 16 is deformed. This is the case where the lower side of FIG. 1 is mainly the vertical lower side as described above. On the other hand, when the upper side in FIG. 1 is mainly a vertical lower side, a force is applied to a thin film such as the immune isolation film 18, that is, the immune isolation film 18 is poured in a deformed state.

  As a result, the cell distribution of the cell suspension is biased, and the function and viability of the cells are reduced due to lack of oxygen and nutrients. For example, when the cells to be introduced into the cell chamber 17 are adherent cells, the cells settle on the membrane in a state where the cells gather by gravity in the recesses of the oxygen permeable membrane 16 and the immunoisolation membrane 18 resulting from the deformation. A large number of cells are distributed in the center of the membrane, and there are few cells in the periphery. Further, even in the case where cells are introduced into the cell chamber 17 in the form of a suspension and then gelled and confined (for example, a polylactic acid-based injectable gel), the oxygen permeable membrane 16 and the When the cells are gelled in a state where the cells are gathered by gravity in the concave portion, a large number of cells are located in the central portion of the membrane and a small number of cells are located in the peripheral portion.

  Therefore, a bending suppression member 19 (see FIGS. 2 and 3) for suppressing bending of at least the lower side of the cell chamber 17 among the oxygen permeable membrane 16 and the immunoisolation membrane 18 is provided in the cell storage device 1 for transplantation. To do. Here, since the human or animal transplanted with the cell storage device 1 for transplantation is active, even if the cell storage device 1 for transplantation is transplanted with the “lower side” in FIG. The oxygen permeable membrane 16 is not positioned vertically below the cell chamber 17 while the patient or the like transplanted with the cell storage device 1 is generally standing or sitting, although the cell 16 is not positioned vertically below the cell chamber 17. If it is located, at least the deflection suppressing member 19 is provided on the oxygen-permeable film 16. Similarly, if the immune isolation membrane 18 is positioned vertically below the cell compartment 17 in a generally standing or sitting state, at least the immunoisolation membrane 18 is provided with a deflection suppressing member 19.

  First, FIG. 2 is an enlarged vertical sectional view of the oxygen permeable film 16 or the immunoisolation film 18 showing an example in which the deflection suppressing member 19 is embedded in the oxygen permeable film 16 or the immunoisolation film 18. As shown in FIG. 2, the deflection suppressing member 19 may be provided dispersed in the oxygen permeable membrane 16 or the immunoisolation membrane 18 so as not to hinder the function of the oxygen permeable membrane 16 or the immunoisolation membrane 18. Alternatively, the deflection suppressing member 19 may be formed of a porous material or the like so as not to impair the function of the oxygen permeable membrane 16 or the immunoisolation membrane 18. In the latter case, the deflection suppressing member 19 may be formed over the entire width of the oxygen permeable membrane 16 or the immunoisolation membrane 18 in the width direction.

  FIG. 3 is an enlarged vertical cross-sectional view of a case where a membrane-shaped deflection suppressing member 19 is formed on the oxygen permeable membrane 16 or the immunoisolation membrane 18 from below. That is, as shown in FIG. 3, a deflection suppressing member 19, which is a supporting film for supporting from below, is formed on the oxygen permeable membrane 16 or the immunoisolation membrane 18, and the end portion is formed on the inner peripheral surface 13a of the housing 11. May be supported. Also in this case, the function of the oxygen permeable membrane 16 or the immunoisolation membrane 18 is not inhibited. Specifically, the deflection suppressing member 19 serving as a support film may cover portions of the oxygen permeable film 16 or the immunoisolation film 18. Alternatively, the deflection suppressing member 19 as a support film may be formed of a porous material.

  More specifically, when a silicon-based material is used as the oxygen-permeable film 16, the elastomer is cured while being impregnated in a porous film such as a nonwoven fabric, so that the deflection suppressing member 19 serving as a support film is formed. Can be. As the immunoisolation membrane 18, a laminate obtained by laminating a porous film on the immunoisolation membrane 18 as the deflection suppressing member 19 as a support membrane can be used.

  FIG. 4 is a block diagram showing a schematic configuration of a transplant cell storage system 21 including the transplant cell storage device 1. The transplant cell storage system 21 includes the transplant cell storage device 1 and an oxygen supply device 22. The oxygen supply device 22 includes a pump 24 that takes in and supplies outside air via a pipe 23, and a pipe 25 that connects the discharge side of the pump 24 and the introduction flow path 14 of the cell storage device 1 for transplantation. I have. The pump 24 is driven based on the control of the control unit 26. Although not shown, the pump 24 and the control unit 26 are driven by using a primary battery or a secondary battery or the like incorporated in the oxygen supply device 22 as a power supply.

  The cell storage device for transplantation 1 is transplanted into a living body transplant destination tissue 100, and a pipe 23 extends from the transplant destination tissue 100 to the outside of the living body. Further, a pipe 27 connected to the discharge channel 15 also extends outside the living body from the transplantation target tissue 100. The oxygen supply device 22 does not supply pure oxygen to the transplant cell storage device 1, but takes in air from a pipe 23 by a pump 24 and supplies the air to the transplant cell storage device 1 via a pipe 25. Therefore, the gas supplied to the cavity 13 includes gas components in the air, such as nitrogen, in addition to oxygen. In addition, it is desirable to provide a filter in the pipes 23 and 27 so that foreign substances such as dust in the air do not enter the hollow portion 13 as much as possible.

Next, the function and effect of the transplant cell storage device 1 and the transplant cell storage system 21 will be described.
Here, an example in which cells of pancreatic islets are stored in the cell storage device 1 for transplantation and type 1 diabetes is treated will be described. In the transplant cell storage system 21, the cells of the pancreatic islet are stored in the cell chamber 17 of the cell storage device 1 for transplantation, and the cell storage device 1 for transplantation is transplanted into the transplant destination tissue 100 of the living body. In this state, one ends of the pipes 25 and 27 are connected to the cell storage device 1 for transplantation, and the other ends extend outside the living body.

The oxygen supply device 22 is a relatively portable device, and a patient using the transplant cell storage system 21 can attach the oxygen supply device 22 to his / her lumbar region or the like and attach the transplant cell storage system 21 to its own body. It can be moved with it attached. A pipe 25 is connected to the oxygen supply device 22. Then, under the control of the control unit 26, the pump 24 is driven to take in air containing oxygen from the pipe 23 and send it to the cavity 13 of the cell storage device 1 for transplantation. The sent oxygen in the air passes through the oxygen permeable membrane 16 and is supplied to the cells of the pancreatic islets.
On the other hand, since the oxygen permeable membrane 16 separates the cavity 13 from the cell chamber 17, foreign matter such as fine dust that has entered together with air from the introduction channel 14 is shut down by the oxygen permeable membrane 16, 17 cannot enter.

  Except for carbon dioxide discharged from the pancreatic islets in the cell chamber 17 (flowing into the cell chamber 17 through the oxygen permeable membrane 16), oxygen remaining without being consumed in the pancreatic islets, and oxygen in the air introduced into the cavity 13 Gases such as nitrogen are discharged outside the body. That is, when new gases are introduced into the cavity 13 from the introduction channel 14, these gases are discharged from the cavity 13 through the discharge channel 15 to the outside of the living body by negative pressure. The metabolites of the cells of the pancreatic islets in the cell compartment 17 penetrate the immune isolating membrane 18. In addition, the cells of the pancreatic islets in the cell compartment 17 absorb nutrient components from the body fluid or the like of the living body via the immune isolation membrane 18. The pancreatic islets in the cell compartment 17 secrete insulin, which is absorbed into the patient's body by permeating the immune isolating membrane 18, thereby exerting a therapeutic effect on patients with type 1 diabetes. Can be.

  According to the transplant cell storage device 1 and the transplant cell storage system 21, the lower membrane of the oxygen permeable membrane 16 and the immunoisolation membrane 18 is supported by the deflection suppressing member 19. Therefore, the oxygen permeable membrane 16 or the immunoisolation membrane 18 does not bend due to the weight of the pancreatic islet cells or the like in the cell chamber 17. Therefore, the cells of the pancreatic islets and the like in the cell chamber 17 are not biased to one place, and the cells are evenly arranged on the oxygen permeable membrane 16 or the immunoisolation membrane 18 in the cell chamber 17. Therefore, oxygen and nutrients can be evenly supplied to the cells.

[Experimental example 1]
As an experimental example, the cellulosic nonwoven fabric was cured while being impregnated with the silicone adhesive 7-9900 to form the oxygen permeable membrane 16 in which the deflection suppressing member 19 was embedded. This was adhered to the casing 11 formed using a 3D printer, and the cell suspension was introduced onto the oxygen permeable membrane 16. Then, when visually observed, no deformation of the oxygen-permeable film was observed.

[Experimental example 2]
An example in which the immunoisolation membrane 18 includes a nonwoven fabric-like deflection suppressing member 19 was examined. A porous PTFE membrane (immunoisolation membrane 18) laminated with Allentown polyester nonwoven fabric Reemay (registered trademark) is adhered to the housing 11, and the cell suspension is placed on the immunoisolation membrane 18 in the cell compartment 17. Was introduced. In this case, no deformation of the immunoisolation membrane 18 was observed visually.

  The following Examples 2 to 6 are different from Example 1 only in the configuration of the deflection suppressing member 19. Therefore, the same reference numerals are used for members and the like common to the first embodiment, and detailed description is omitted. Embodiments 2 to 6 are all related to the bending suppression member 19 that supports the oxygen permeable membrane 16 which is the membrane below the cell chamber 17.

FIG. 5 is a longitudinal sectional view of the transplant cell storage device 1 according to the second embodiment. In the hollow portion 13, the inner wall surface 13 b of the hollow portion 13 extends from between the outlet of the introduction flow channel 14 and the inlet of the discharge flow channel 15, and its tip 19 a contacts the oxygen permeable membrane 16. A deflection suppressing member 19 that supports the oxygen permeable film 16 is provided. In the examples of the second to sixth embodiments, only one bending suppression member 19 supports the oxygen permeable membrane 16, but a plurality of bending suppression members 19 are provided, and a plurality of bending suppression members 19 are provided. The oxygen permeable film 16 may be supported.
In the example of FIG. 5, the tip 19 a of the deflection suppressing member 19 suppresses the deflection of the oxygen permeable film 16. Therefore, the cells of the pancreatic islets in the cell chamber 17 are not biased to one place, and the cells are evenly arranged on the oxygen permeable membrane 16 in the cell chamber 17. Thus, oxygen and nutrients can be evenly supplied to the cells of the pancreatic islets.

  FIG. 6 is a plan view of the cavity 13. The deflection suppressing member 19 has a rectangular shape in a top view, and a direction connecting an inlet of the introduction flow path 14 and an outlet of the discharge flow path 15 is a short side direction of the rectangular shape. As indicated by an arrow 29, the oxygen introduced into the cavity 13 from the inlet of the introduction flow path 14 flows in the cavity 13, bypassing the deflection suppressing member 19 in many cases, and flows into the outlet of the discharge flow path 15. I reach you.

  Here, FIG. 12 is a plan view of the cavity 13 in a case where the deflection suppressing member 19 which is a comparative example of FIG. 6 is not provided. In this case, since there is no obstacle such as the deflection suppressing member 19, oxygen introduced into the hollow portion 13 from the inlet of the introduction flow path 14 flows through the inlet of the introduction flow path 14 and the outlet of the discharge flow path 15. Are easily discharged from the discharge flow path 15 through a route indicated by an arrow 111 connecting the two at a straight line distance. Therefore, sufficient oxygen is supplied to the pancreatic islet cells in the cell chamber 17 located immediately below the oxygen-permeable membrane 16 in the vicinity of a route connecting the inlet of the introduction channel 14 and the outlet of the discharge channel 15 at a linear distance. Is done. However, there is a possibility that sufficient oxygen is not supplied to the cells of the pancreatic islets in the cell chamber 17 immediately below the oxygen permeable membrane 16 near the inner peripheral surface 13a of the cavity 13 far from the route.

  Compared to the case of the comparative example, in the examples of FIGS. 5 and 6, the oxygen introduced from the inlet of the introduction flow path 14 flows around by the deflection suppressing member 19 as shown by an arrow 29. Therefore, the pancreatic islets in the cell compartment 17 immediately below the oxygen permeable membrane 16 near the inner peripheral surface 13a of the cavity 13 far from the vicinity of the route connecting the inlet of the introduction flow channel 14 and the outlet of the discharge flow channel 15 at a linear distance. Cells can be supplied with sufficient oxygen.

[Example of experiment]
After forming the housing 11 having the deflection suppressing member 19 using a 3D printer, the oxygen permeable membrane 16 was bonded using an adhesive, and the cell suspension was introduced onto the oxygen permeable membrane 16. In this case, the deformation of the oxygen permeable film 16 was not visually observed.

FIG. 7 is a vertical cross-sectional view of the transplant cell storage device 1 according to the third embodiment. The third embodiment differs from the second embodiment in that the deflection suppressing member 19 has a tapered shape toward the distal end 19a.
Also in the example of FIG. 7, the tip 19 a of the bending suppression member 19 suppresses the bending of the oxygen permeable film 16. Therefore, the cells of the pancreatic islets in the cell room 17 are not biased to one place, and the cells of the pancreatic islets are evenly arranged on the oxygen-permeable membrane 16 of the cell room 17. Thus, oxygen and nutrients can be evenly supplied to the cells of the pancreatic islets.

In the second embodiment, the tip 19 a of the deflection suppressing member 19 is in contact with the oxygen permeable film 16. Therefore, there is no oxygen passing through a route immediately adjacent to the inlet of the introduction channel 14 and the outlet of the discharge channel 15. All oxygen that has flowed into the cavity 13 from the introduction flow path 14 passes through a detour route as shown by an arrow 29 in FIG. 6, and oxygen in the cavity 13 is efficiently distributed evenly to the whole cells of the pancreatic islet in the cell compartment 17. It becomes easy to supply.
However, since the tip 19a of the deflection suppressing member 19 is in contact with the oxygen permeable membrane 16, oxygen is less likely to pass through the cells of the pancreatic islet existing immediately below the portion of the oxygen permeable membrane 16 with which the tip 19a is in contact. The possibility arises.

  However, in the second embodiment, since the deflection suppressing member 19 has a tapered shape toward the tip 19a, the area of the portion of the oxygen permeable membrane 16 in contact with the tip 19a can be reduced. Therefore, the area of the cell chamber 17 immediately below the portion of the oxygen permeable membrane 16 with which the tip 19a is in contact can be reduced, so that it is possible to suppress the difficulty of oxygen from spreading to cells of the pancreatic islet existing in the portion. .

FIG. 8 is a longitudinal sectional view of the transplant cell storage device 1 according to the fourth embodiment. The fourth embodiment differs from the second embodiment in that the deflection suppressing member 19 is formed of a porous material.
Also in the example of FIG. 8, the tip 19 a of the deflection suppressing member 19 suppresses the deflection of the oxygen permeable film 16. Therefore, the cells of the pancreatic islets in the cell room 17 are not biased to one place, and the cells of the pancreatic islets are evenly arranged on the oxygen-permeable membrane 16 of the cell room 17. Thus, oxygen and nutrients can be evenly supplied to the cells of the pancreatic islets.

Further, as in the second embodiment, in the fourth embodiment, the tip 19 a of the deflection suppressing member 19 is in contact with the oxygen permeable film 16. Therefore, there is no oxygen passing through a route immediately adjacent to the inlet of the introduction channel 14 and the outlet of the discharge channel 15. All the oxygen that has flowed into the cavity 13 from the introduction flow path 14 passes through a large detour route as shown by the arrow 29 in FIG. 6, and the oxygen in the cavity 13 efficiently spreads to the entire pancreatic islet cells in the cell chamber 17. It becomes easy to supply evenly.
However, since the tip 19a of the deflection suppressing member 19 is in contact with the oxygen permeable membrane 16, oxygen does not easily spread to the cells of the pancreatic islet existing immediately below the portion of the oxygen permeable membrane 16 with which the tip 19a is in contact. The possibility arises.

  However, in the fourth embodiment, the deflection suppressing member 19 is formed of a porous material. Therefore, the oxygen in the cavity 13 passes through the hole formed in the porous material, passes through the portion of the oxygen permeable membrane 16 where the tip 19a of the deflection suppressing member 19 is in contact with the cell chamber 17 immediately below the portion. The cells of the islets are supplied with sufficient oxygen. Therefore, even if the tip 19a of the deflection suppressing member 19 is in contact with the oxygen permeable membrane 16, it is possible to suppress the oxygen from hardly permeating the cells of the pancreatic islet in the portion.

FIG. 9 is a plan view of the hollow portion 13 of the transplant cell storage device 1 according to the fifth embodiment. The fifth embodiment is different from the second embodiment in the following point. That is, compared with the vicinity 19d where the deflection suppressing member 19 connects the entrance of the introduction flow path 14 and the exit of the discharge flow path 15 in the immediate vicinity, the other parts are the entrance of the introduction flow path 14 and the discharge flow path. The width in the direction (the direction of arrow 111 in FIG. 12) connecting to the 15 outlets is formed short. That is, the shape of the deflection suppressing member 19 shown in FIG. 9 in a plan view is similar to the shape in the horizontal direction of FIG. 6 near the position 19d where the inlet of the introduction flow path 14 and the outlet of the discharge flow path 15 are directly connected. Long width. On the other hand, the width in the left-right direction of FIG. 9 gradually decreases as the distance from the closest connection position increases. In the example shown in FIG. 9, the deflection suppressing member 19 has a rhombic shape in plan view. However, Embodiment 4 does not limit the shape to a rhombus.
Also in the example of FIG. 9, the tip 19 a of the bending suppression member 19 suppresses the bending of the oxygen permeable film 16. Therefore, the cells of the pancreatic islets in the cell room 17 are not biased to one place, and the cells of the pancreatic islets are evenly arranged on the oxygen-permeable membrane 16 of the cell room 17. Thus, oxygen and nutrients can be evenly supplied to the cells of the pancreatic islets.

  In the fifth embodiment, the area of the distal end 19a (see FIG. 5) of the deflection suppressing member 19 is reduced on both ends 19c in a direction orthogonal to the direction connecting the inlet of the introduction flow path 14 and the outlet of the discharge flow path 15. Will be. Thus, as is apparent from a comparison between FIG. 6 and FIG. 9, in the fifth embodiment, the area of the tip 19a of the deflection suppressing member 19 can be reduced as a whole. Therefore, even when the tip 19a of the deflection suppressing member 19 is in contact with the oxygen permeable membrane 16, the area of the cell chamber 17 immediately below the contact portion of the oxygen permeable membrane 16 can be limited, and oxygen is supplied to the cells of the pancreatic islet located immediately below. This makes it possible to suppress difficulty in passing.

FIG. 10 is a plan view of the hollow portion 13 of the transplant cell storage device 1 according to the sixth embodiment. The sixth embodiment differs from the second embodiment in the following point. That is, compared with the vicinity 19d where the deflection suppressing member 19 connects the entrance of the introduction flow path 14 and the exit of the discharge flow path 15 in the immediate vicinity, the other parts are the entrance of the introduction flow path 14 and the discharge flow path. The width in the direction (the direction of arrow 111 in FIG. 12) connecting to the 15 outlets is formed long. That is, the shape of the deflection suppressing member 19 shown in FIG. 10 when viewed in a plan view is near the position 19d connecting the inlet of the introduction flow path 14 and the outlet of the discharge flow path 15 in the immediate vicinity. Short width. On the other hand, the width in the left-right direction in FIG. 10 is long at both end portions 19b farthest from the position of the closest connection. In the example shown in FIG. 10, the deflection suppressing member 19 has an H-shape when viewed in plan. However, Embodiment 5 does not limit the shape to the H-shape.
Also in the example of FIG. 10, the tip 19 a of the deflection suppressing member 19 suppresses the deflection of the oxygen permeable film 16. Therefore, the cells of the pancreatic islets in the cell room 17 are not biased to one place, and the cells of the pancreatic islets are evenly arranged on the oxygen-permeable membrane 16 of the cell room 17. Thus, oxygen and nutrients can be evenly supplied to the cells of the pancreatic islets.

  In this case, the flow of oxygen from the inlet of the introduction channel 14 to the outlet of the discharge channel 15 is shown in FIG. Since the deflection suppressing member 19 has the above-mentioned shape, the arrow 31 indicating the flow of oxygen also largely detours along the inner peripheral surface 13a. This is apparent from comparison with the arrow 29 in FIG. 6 in the second embodiment. Therefore, according to the sixth embodiment, it becomes possible to supply oxygen evenly to pancreatic islet cells distributed over a wide range of the cell compartment 17.

  However, in the sixth embodiment, when the tip 19a (see FIG. 5) of the deflection suppressing member 19 is brought into contact with the oxygen permeable film 16 as is clear from FIG. 10 compared with FIGS. The area of the cell chamber 17 immediately below the space tends to be large. Therefore, there is a possibility that sufficient oxygen cannot be supplied to the pancreatic islets in the cell compartment 17 at that point. Therefore, when the tip 19a (see FIG. 5) of the deflection suppressing member 19 is brought into contact with the oxygen permeable membrane 16, the bending suppressing member 19 of the sixth embodiment has a tapered tip 19a as in the third embodiment, or It is desirable that the deflection suppressing member 19 be made of a porous material as in the fourth embodiment.

  FIG. 11 is an exploded perspective view of the transplant cell storage device 1 according to the seventh embodiment. In the seventh embodiment, members common to the first embodiment are denoted by the same reference numerals as those in the first embodiment, and the detailed description is omitted.

  The cell storage device 1 for transplantation of Example 7 includes a housing 11 that is a flat and wide cylinder, and immunoisolation membranes 18 that cover the upper and lower openings of the housing 11, respectively. The transplant cell storage device 1 of the present embodiment differs from the first to sixth embodiments in that it does not include the oxygen permeable membrane 16, the cavity 13, and the like. This is because some cells do not need oxygen supply. The inside of the housing 11 is a cell room 17.

  Further, a bending suppressing member 19 is provided for suppressing bending of a film which may be at least below the cell chamber 17 among the two immunoisolation films 18. In the example of FIG. 11, a deflection suppressing member 19 is provided on the immunoisolation film 18 on the lower side in FIG. 11 by the method of FIG. 2 or 3 in the first embodiment. As a matter of course, the deflection suppressing member 19 may be provided on the upper side of the immune isolation film 18 in FIG. 11 by the method of FIG. 2 or 3 in the first embodiment.

  According to the present embodiment, the immune isolation membrane 18 is supported by the deflection suppressing member 19. Therefore, the immune isolation film 18 does not bend due to the weight of the cells and the like in the cell chamber 17. Therefore, the cells and the like in the cell room 17 are not biased to one place, and the cells are evenly arranged on the immunoisolation membrane 18 in the cell room 17. Therefore, nutrients can be evenly supplied to the cells.

Note that the present invention is not limited to the above-described embodiment, and includes various modifications. For example, the above-described embodiments have been described in detail in order to explain the present invention in an easy-to-understand manner, and are not necessarily limited to those having all the configurations described above.
Further, a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of one embodiment can be added to the configuration of another embodiment. Further, for a part of the configuration of each embodiment, it is also possible to add / delete / replace another configuration.

REFERENCE SIGNS LIST 1 cell transplanting device for transplantation 11 housing 13 cavity 13 b inner wall surface 14 introduction channel 15 discharge channel 17 cell room 16 oxygen permeable membrane 18 immunoisolation membrane 19 deflection suppressing member 19 a tip 21 cell transplanting system 22 oxygen supply device

Claims (10)

A housing,
A cavity formed inside the housing,
An introduction flow path connected to the cavity and introducing oxygen from the outside into the cavity,
A discharge channel connected to the hollow portion and discharging gas in the hollow portion,
A cell chamber formed inside the housing and containing cells,
An oxygen-permeable membrane provided in the housing to partition the cavity and the cell chamber,
An immune isolation membrane provided in the housing so as to close the outside of the cell chamber,
A bending suppression member that suppresses bending of a membrane that may be below the cell chamber of the oxygen permeable membrane and the immune isolation membrane,
A cell storage device for transplantation, which is transplanted into a living body.   The cell storage device for transplantation according to claim 1, wherein the deflection suppressing member is embedded in a membrane of the oxygen permeable membrane and the immunoisolation membrane that may be below the cell chamber.   The deflection suppressing member is a support film that supports a lower one of the cell chambers of the oxygen permeable membrane and the immune isolation membrane from below, and an end of the support member is supported on an inner peripheral surface of the housing. The cell storage device for transplant according to claim 1, wherein the device is used.   The deflection suppressing member extends from between the outlet of the introduction flow path and the inlet of the discharge flow path on the inner wall surface in the cavity, and the tip thereof is in contact with the oxygen permeable membrane, so that the oxygen permeable membrane is The cell storage device for transplantation according to claim 1, wherein the cell storage device supports the cell.   The cell storage device for transplant according to claim 4, wherein a tip of the deflection suppressing member is tapered toward the oxygen permeable membrane.   The cell storage device for transplant according to claim 4, wherein the deflection suppressing member is formed of a porous material.   The deflection suppressing member is characterized in that a width in a direction connecting the outlet and the inlet is shorter than that near a position connecting the outlet and the inlet immediately. The transplant cell storage device according to claim 4.   The deflection suppressing member is characterized in that a width in a direction connecting the outlet and the inlet is longer than that in a vicinity of a position connecting the outlet and the inlet in the immediate vicinity. The transplant cell storage device according to claim 4. A housing,
A cell chamber formed inside the housing and containing cells,
An immunoisolation membrane covering the openings on both sides of the cell compartment,
A flexure suppressing member that suppresses flexure of the membrane below the cell chamber of the two immunoisolation membranes,
A cell storage device for transplantation, which is transplanted into a living body. A cell storage device for transplantation according to any one of claims 1 to 8,
A transplant cell storage system comprising: an oxygen supply device connected to the introduction channel of the transplant cell storage device by a pipe and supplying oxygen to the cavity via the introduction channel.

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