JP2020010618A - Housing device of cells for transplantation, and housing system of cells for transplantation - Google Patents

Housing device of cells for transplantation, and housing system of cells for transplantation Download PDF

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JP2020010618A
JP2020010618A JP2018133830A JP2018133830A JP2020010618A JP 2020010618 A JP2020010618 A JP 2020010618A JP 2018133830 A JP2018133830 A JP 2018133830A JP 2018133830 A JP2018133830 A JP 2018133830A JP 2020010618 A JP2020010618 A JP 2020010618A
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transplantation
housing
cells
storage device
cell storage
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優史 丸山
Yuji Maruyama
優史 丸山
正樹 松森
Masaki Matsumori
正樹 松森
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Hitachi Ltd
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Hitachi Ltd
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Priority to PCT/JP2019/023372 priority patent/WO2020017195A1/en
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Abstract

To provide a housing device of cells for transplantation, a housing system of cells for transplantation and a method for transplanting a housing device of cells for transplantation in which a possibility of coming off of a piping connected to the housing device of cells for transplantation can be reduced.SOLUTION: A housing device comprises: a step part 16 which is provided outside on the opposite side of an immunity isolating membrane 14 side of an enclosure 11, and is higher than the enclosure 11 while forming a step; an introduction flow path 17 which is a flow channel penetrating from a tip end 16a of the step part 16 to a hollow part 13 and feeds oxygen into the hollow part 13 from outside; and an exhaust gas flow channel 18 which is a flow path penetrating from the tip end 16a of the step part 16 to the hollow part 13, and discharges exhaust gas inside the hollow part 13 to the outside.SELECTED DRAWING: Figure 1

Description

本発明は、移植用細胞収容装置及び移植用細胞収容システムに関する。   The present invention relates to a transplant cell storage device and a transplant cell storage system.

本技術分野の背景技術として、特開2004−147555号公報(特許文献1)がある。この公報には、「酸素透過性材料からなり、内部に細胞が固着され且つ培養液が灌流される培養液用流路構造を有する少なくとも2つの細胞培養チャンバーが積層され、各細胞培養チャンバー間の少なくとも1カ所に、酸素透過性材料からなる気体用流路構造が設けられ、各チャンバーを積層面に対して垂直方向に接続し、前記培養液用流路構造に培養液を灌流させるための培養液灌流路を備える細胞培養装置。」と記載されている(要約参照)。   As a background art of this technical field, there is Japanese Patent Application Laid-Open No. 2004-147555 (Patent Document 1). This publication states that "at least two cell culture chambers each having a flow path structure for a culture solution formed of an oxygen-permeable material, in which cells are fixed and a culture solution is perfused, are laminated, and between each cell culture chamber. A gas flow path structure made of an oxygen-permeable material is provided in at least one place, and each chamber is connected in a direction perpendicular to the lamination surface, and culture for perfusing a culture solution into the culture liquid flow path structure is performed. A cell culture device provided with a liquid perfusion channel "(see abstract).

特開2004−147555号公報JP-A-2004-147555

前記特許文献1には、細胞を培養する装置内に酸素を供給する気体用流路構造が記載されている。しかし、特許文献1の技術は細胞を収容して生体内に移植する移植用細胞収容装置ではないため、細胞を収容する装置に酸素を供給し、同装置から排気を排出させる配管と同装置との接続部分が外れる可能性については考慮されていないという不具合がある。
そこで、本発明は、移植用細胞収容装置に接続する配管が外れる可能性を低減することができる移植用細胞収容装置及び移植用細胞収容システムを提供することを課題とする。
Patent Document 1 describes a gas flow path structure for supplying oxygen into an apparatus for culturing cells. However, the technique disclosed in Patent Document 1 is not a transplant cell storage device that stores cells and transplants them into a living body. Therefore, a pipe that supplies oxygen to a device that stores cells and discharges exhaust gas from the device is used. There is a problem that the possibility of disconnection of the connection is not considered.
Accordingly, an object of the present invention is to provide a cell storage device for transplantation and a cell storage system for transplantation, which can reduce the possibility of disconnection of a pipe connected to the cell storage device for transplantation.

上記課題を解決するため、本発明の一形態である移植用細胞収容装置は、一方に開口部が形成された筐体と、前記筐体の内部の空間を仕切って当該筐体内に空洞部を形成する酸素透過膜と、前記酸素透過膜の前記空洞部側とは反対側で前記開口部を覆うように形成された免疫隔離膜と、前記酸素透過膜と前記免疫隔離膜とによって囲まれた細胞室と、前記筐体の前記免疫隔離膜側とは反対側の面に設けられ当該面よりも段差をなして高くなっている段差部と、前記段差部の先端から前記空洞部までを貫く流路であり当該空洞部内に酸素を外部から供給する導入流路と、前記段差部の先端から前記空洞部までを貫く流路であり当該空洞部内の排気を外部に排出する排気流路とを備え、生体内に移植されることを特徴とする。   In order to solve the above-mentioned problems, a cell housing device for transplantation, which is an embodiment of the present invention, includes a housing having an opening formed on one side thereof, and a cavity formed in the housing by partitioning a space inside the housing. An oxygen permeable membrane to be formed, an immunoisolation membrane formed to cover the opening on the side opposite to the cavity side of the oxygen permeable membrane, and surrounded by the oxygen permeable membrane and the immunoisolation membrane A cell room, a step portion provided on a surface of the housing opposite to the immunoisolation membrane side, and a step portion higher than the surface, and penetrating from the tip of the step portion to the hollow portion. An introduction flow path that is a flow path and supplies oxygen into the cavity from outside, and an exhaust flow path that is a flow path that penetrates from the tip of the step portion to the cavity and discharges exhaust gas in the cavity to the outside. And is implanted in a living body.

本発明によれば、移植用細胞収容装置に接続する配管が外れる可能性を低減することができる移植用細胞収容装置及び移植用細胞収容システムを提供することができる。
上記した以外の課題、構成及び効果は、以下の実施形態の説明により明らかにされる。
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 reduce the possibility of disconnection of a pipe connected to the transplant cell storage device.
Problems, configurations, and effects other than those described above will be apparent from the following description of the embodiments.

本発明の一実施例に係る移植用細胞収容装置の縦断面図である。It is a longitudinal cross-sectional view of the cell storage device for transplantation which concerns on one Example of this invention. 本発明の一実施例に係る移植用細胞収容システムの構成を示すブロック図である。It is a block diagram showing the composition of the cell storage system for transplantation concerning one example of the present invention. 本発明の一実施例に係る移植用細胞収容装置を生体の移植先組織内に移植した状態の縦断面図である。BRIEF DESCRIPTION OF THE DRAWINGS It is a longitudinal cross-sectional view of the state which transplanted the cell storage device for transplantation which concerns on one Example of this invention in the transplantation destination tissue of a living body. 本発明の一実施例に係る移植用細胞収容装置を生体の移植先組織内に移植した状態における他の例の縦断面図である。It is a longitudinal section of another example in the state where the cell storage device for transplantation concerning one example of the present invention was transplanted in the transplantation target tissue of the living body.

以下、本発明の実施例について図面を用いて説明する。
移植用細胞収容装置は、内部に所定の細胞を収容した状態で人間や動物の生体内に移植して、当該細胞が分泌する分泌物によって医療効果を発揮するようにした装置である。
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.

典型的な例を説明すると、移植用細胞収容装置内に脳死状態の人体から摘出して得られた、あるいは、iPS細胞(induced Pluripotent Stem cells)由来である膵島の細胞を収容して人体に埋め込んで用いる例が挙げられる。これにより、当該膵島が分泌するインスリンによって1型糖尿病を治療することができる。   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.

このような移植用細胞収容装置に関連する技術としては、前記特許文献1に開示のものが知られている。すなわち、特許文献1には、細胞を培養する装置内に酸素を供給する気体用流路構造が記載されている。しかし、特許文献1の技術は、細胞を収容して生体内に移植する移植用細胞収容装置ではないため、細胞を収容する装置に酸素を供給し、同装置から排気を排出させる各配管と同装置との接続部分が外れる可能性については考慮されていないという不具合がある。   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 gas flow path structure for supplying oxygen into an apparatus for culturing cells. However, the technique disclosed in Patent Document 1 is not a transplant cell storage device that stores cells and transplants them into a living body. Therefore, the technique of supplying oxygen to the device that stores cells and discharging exhaust gas from the device is the same as that of the piping. There is a problem in that the possibility of disconnection with the device is not considered.

すなわち、移植用細胞収容装置には、特許文献1の技術とは異なり、その内部に酸素を供給し、また、その内部からの排気を外部に排出する配管を接続する必要がある。しかし、移植用細胞収容装置と配管との接続部分が生体(人間又は動物)の皮下組織内に存在する場合は、生体が動くことにより生体から応力を受けることなる。そして、この応力によって、移植用細胞収容装置と配管とが外れてしまう恐れがあるという不具合がある。
そこで、以下では、移植用細胞収容装置と配管との接続が外れてしまう可能性を低減することができる発明の実施形態について説明する。
That is, unlike the technique of Patent Document 1, it is necessary to connect a pipe that supplies oxygen to the inside and exhausts exhaust air from the inside to the outside, unlike the technique of Patent Document 1. However, when the connecting portion between the cell storage device for transplantation and the pipe exists in the subcutaneous tissue of a living body (human or animal), the living body receives stress from the living body due to movement. Then, there is a problem that the stress may cause the cell storage device for transplantation and the pipe to come off.
Therefore, an embodiment of the invention that can reduce the possibility of disconnection between the cell storage device for transplantation and the pipe will be described below.

図1は、本発明の一実施形態である移植用細胞収容装置1の縦断面図である。移植用細胞収容装置1は、筐体11を備えている。筐体11は図1の上側から視た形状が円形でもよいし、長方形状でもよいし、その他、様々な形状をとることができる。筐体11の内部は空間になっており、筐体11の一方(図1で下側)は開口部11aをなしている。筐体11の材料としては、生体に悪影響のない材料であれば様々な材料を用いることができるが、一例を挙げれば樹脂を用いることができる。なお、樹脂も含め、筐体11の材料としては疎水性の高い材料であることが望ましい。生体内に移植したときに生体側から体液が筐体11に沁み込まないようにするためである。
筐体11の内部の空間を仕切るように酸素透過膜12が設けられている。酸素透過膜12は、その一方の面の外周縁部分が、筐体11内部の空間の図1における中間高さにある段部11bに接着等により接合されている。
FIG. 1 is a longitudinal sectional view of a transplant cell storage device 1 according to one embodiment of the present invention. The cell storage device 1 for transplantation has a housing 11. The shape of the housing 11 as viewed from above in FIG. 1 may be circular, rectangular, or various other shapes. The inside of the housing 11 is a space, and one side (the lower side in FIG. 1) of the housing 11 forms an opening 11a. Various materials can be used as the material of the housing 11 as long as the material does not adversely affect the living body. For example, a resin can be used. It is desirable that the material of the housing 11 including the resin is a material having high hydrophobicity. This is to prevent body fluid from penetrating the housing 11 from the living body side when implanted in the living body.
An oxygen permeable film 12 is provided so as to partition the space inside the housing 11. The oxygen permeable membrane 12 has an outer peripheral edge portion on one surface thereof bonded to a step portion 11b at an intermediate height in FIG.

酸素透過膜12は、細胞や体液等の水分は通過させないが酸素は透過させる性質を有する膜である。酸素透過膜12としては、酸素の透過係数がある程度大きな材料であれば様々な材料を使用できるが、例えばシリコーンなどを用いることができる。また、物理的に微細な孔が空いている膜を酸素透過膜として用いることもできる。例えば、W.L.Gore&Associates,Incが開発したePTFE(expanded polytetrafluoroethylene)膜や、PTFE(polytetrafluoroethylene)不織布などは、疎水性が高いため水分が沁み込みにくく、水分と接した状態でも酸素透過膜12として機能する。
筐体11内の空間が酸素透過膜12で仕切られることによって、当該空間の図1における上部の空間は、筐体11の内周面と酸素透過膜12とで囲まれた空間である空洞部13を形成する。
The oxygen permeable membrane 12 is a membrane that does not allow moisture such as cells and body fluids to pass therethrough but allows oxygen to permeate. As the oxygen permeable film 12, various materials can be used as long as the material has a somewhat high oxygen permeability coefficient. For example, silicone can be used. Further, a film having physically fine holes can be used as the oxygen permeable film. For example, an ePTFE (expanded polytetrafluoroethylene) membrane or a PTFE (polytetrafluoroethylene) nonwoven fabric developed by WLGore & Associates, Inc. has high hydrophobicity, so that moisture hardly permeates, and functions as the oxygen permeable membrane 12 even in contact with moisture.
When the space in the housing 11 is partitioned by the oxygen permeable film 12, the upper space of the space in FIG. 1 is a hollow portion that is a space surrounded by the inner peripheral surface of the housing 11 and the oxygen permeable film 12. 13 is formed.

酸素透過膜12の空洞部13側とは反対側(図1において下側)には、筐体11の開口部11aを覆うように免疫隔離膜14が形成されている。免疫隔離膜14は、その一方の面の外周縁部分が筐体11の開口部11aの端縁部11cに接着等によって接合されている。酸素透過膜12と免疫隔離膜14と筐体11の内周面とで囲まれた空間は、細胞室15を形成する。細胞室15は、所定の細胞が収容される空間である。
免疫隔離膜14は、細胞は通過させないが、体液等の水分は通過させる性質を有する膜である。これにより、細胞室15内の細胞は生体の免疫細胞によって攻撃されることが防止され、また、細胞室15内の細胞が移植用細胞収容装置1の外に漏れ出ることも防止される。
On the opposite side (lower side in FIG. 1) of the oxygen permeable membrane 12 from the cavity 13 side, an immune isolation membrane 14 is formed so as to cover the opening 11a of the housing 11. The outer peripheral edge of one surface of the immunoisolation membrane 14 is bonded to the edge 11 c of the opening 11 a of the housing 11 by adhesion or the like. A space surrounded by the oxygen permeable membrane 12, the immune isolation membrane 14, and the inner peripheral surface of the casing 11 forms a cell room 15. The cell room 15 is a space in which predetermined cells are stored.
The immunoisolation membrane 14 is a membrane that has the property of not allowing cells to pass through but passing moisture such as body fluids. This prevents the cells in the cell chamber 15 from being attacked by the immune cells of the living body, and also prevents the cells in the cell chamber 15 from leaking out of the cell storage device 1 for transplantation.

免疫隔離膜14の材料としては、移植先の生体の免疫細胞から細胞室15内の細胞を保護可能で、細胞室15内の細胞が分泌するインスリン等の分泌物が透過して生体側に供与することが可能となる材料であれば限定されない。免疫隔離膜14の材料としては、例えば、多孔質ポリカーボネート、ePTFE膜、PTFE不織布などを挙げることができる。   As a material of the immune isolating membrane 14, cells in the cell chamber 15 can be protected from immune cells of the living body to be transplanted, and secretions such as insulin secreted by the cells in the cell chamber 15 penetrate and are provided to the living body side. The material is not limited as long as the material can be used. Examples of the material of the immunoisolation membrane 14 include a porous polycarbonate, an ePTFE membrane, and a PTFE nonwoven fabric.

筐体11には段差部16が設けられている。段差部16は、筐体11の免疫隔離膜14側とは反対側(図1で上側)の外部に設けられ、筐体11の図1における上面よりも段差をなして高くなっている。段差部16も筐体11同様、生体に悪影響のない材料であれば様々な材料を用いることができるが、一例を挙げれば樹脂を用いることができる。なお、樹脂も含め、段差部16の材料としては疎水性の高い材料であることが望ましい。生体内に移植したときに生体側から体液が段差部16に沁み込まないようにするためである。段差部16は、筐体11と一体成型で形成することができる。段差部16の筐体11からの高さは使用形態によって様々に設定できるが、少なくとも1mm以上の高さを有していることが望ましい。   The housing 11 is provided with a step 16. The step 16 is provided outside the housing 11 on the opposite side (upper side in FIG. 1) from the immunoisolation membrane 14 side, and is higher than the upper surface of the housing 11 in FIG. As with the case 11, various materials can be used for the step portion 16 as long as the material does not adversely affect the living body. For example, a resin can be used. In addition, it is desirable that the material of the step portion 16 including a resin is a material having high hydrophobicity. This is to prevent body fluid from seeping into the step 16 from the living body side when implanted in the living body. The step 16 can be formed integrally with the housing 11. The height of the step portion 16 from the housing 11 can be variously set depending on the usage form, but it is desirable that the height be at least 1 mm or more.

筐体11には、導入流路17が設けられている。導入流路17は、段差部16の先端16aから空洞部13までを貫き、空洞部13内に外部から酸素を供給する流路となる。
筐体11には、排気流路18も設けられている。排気流路18は、段差部16の先端16aから空洞部13までを貫き、空洞部13内の排気を外部に排出する流路となる。
The housing 11 is provided with an introduction channel 17. The introduction channel 17 penetrates from the tip 16 a of the step portion 16 to the cavity 13, and serves as a channel for supplying oxygen from the outside into the cavity 13.
The housing 11 is also provided with an exhaust passage 18. The exhaust passage 18 extends from the tip 16 a of the step 16 to the cavity 13, and serves as a passage for discharging the exhaust gas in the cavity 13 to the outside.

次に、移植用細胞収容装置1を含めた移植用細胞収容システム21について説明する。図2は、移植用細胞収容システム21の構成を示すブロック図である。移植用細胞収容システム21は、移植用細胞収容装置1と酸素供給装置31とを備えている。酸素供給装置31は、導入流路17を介して空洞部13内に酸素を供給する装置である。酸素供給装置31は、配管41を介して外気を取り込んで送給するポンプ32と、このポンプ32の吐出側と移植用細胞収容装置1の導入流路17とを接続する配管42とを備えている。ポンプ32は、制御部33の制御に基づいて駆動する。また、図示はされていないが、ポンプ32及び制御部33は、酸素供給装置31に内蔵されている1次電池又は2次電池等を電源として駆動する。   Next, the transplant cell storage system 21 including the transplant cell storage device 1 will be described. FIG. 2 is a block diagram illustrating a configuration of the cell storage system 21 for transplantation. The transplant cell storage system 21 includes the transplant cell storage device 1 and an oxygen supply device 31. The oxygen supply device 31 is a device that supplies oxygen into the cavity 13 via the introduction flow path 17. The oxygen supply device 31 includes a pump 32 that takes in and supplies outside air via a pipe 41, and a pipe 42 that connects a discharge side of the pump 32 and the introduction channel 17 of the cell storage device 1 for transplantation. I have. The pump 32 is driven based on the control of the control unit 33. Although not shown, the pump 32 and the control unit 33 are driven by using a primary battery, a secondary battery, or the like built in the oxygen supply device 31 as a power supply.

移植用細胞収容装置1は、生体の移植先組織100内に移植されていて、配管42が移植先組織100から生体外部に延びている。また、排気流路18に接続された配管43も移植先組織100から生体外部に延びている。なお、配管43は必ずしも設けなくてもよい。酸素供給装置31は、純粋な酸素を移植用細胞収容装置1に供給するのではなく、ポンプ32によって配管41から空気を取り込んで、配管42を介して移植用細胞収容装置1に供給する。よって、空洞部13に供給する気体には酸素以外にも窒素等、空気中の気体成分が含まれる。なお、配管41,43には、空気中の塵埃等の異物が、極力、空洞部13に入り込まないようにフィルタを設けることが望ましい。配管43を設けないときは排気流路18の出口側にフィルタを設けることが望ましい。   The cell storage device for transplantation 1 is transplanted into a living body transplantation destination tissue 100, and a pipe 42 extends from the transplantation destination tissue 100 to the outside of the living body. Further, a pipe 43 connected to the exhaust passage 18 also extends from the transplant destination tissue 100 to the outside of the living body. Note that the pipe 43 is not necessarily provided. The oxygen supply device 31 does not supply pure oxygen to the transplant cell storage device 1, but takes in air from a pipe 41 by a pump 32 and supplies the air to the transplant cell storage device 1 via a pipe 42. 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 41 and 43 so that foreign matter such as dust in the air does not enter the cavity 13 as much as possible. When the pipe 43 is not provided, it is desirable to provide a filter on the outlet side of the exhaust passage 18.

次に、移植用細胞収容装置1の移植方法について説明する。図3は、移植用細胞収容装置1を生体の移植先組織100内に移植した状態の縦断面図である。図3の例では、移植用細胞収容装置1を生体の移植先組織100内の最も浅い部位に移植した状態を示している。すなわち、移植用細胞収容装置1の筐体11は、移植先組織100における皮膚101の直下の皮下組織102に免疫隔離膜14側を皮下組織102の深い方向側として移植している。そして、図3における筐体11の上面よりも段差部16の高さを利用して高くなっている段差部16の先端16aは生体の移植先組織100の外部に露出させる。移植用細胞収容装置1を皮膚101の直下の皮下組織102に移植する場合でも、人体の皮膚101の厚さを考慮して、段差部16の筐体11からの高さは1mm以上あることが望ましい。この生体の移植先組織100の外部に露出している段差部16の先端16aの導入流路17、排気流路18にそれぞれ配管42,43を接着剤等で接続する。   Next, a transplantation method of the cell storage device 1 for transplantation will be described. FIG. 3 is a longitudinal sectional view of a state where the cell storage device 1 for transplantation is transplanted into a transplantation target tissue 100 of a living body. In the example of FIG. 3, a state is shown in which the cell storage device for transplantation 1 is transplanted to the shallowest site in the transplantation destination tissue 100 of a living body. That is, the casing 11 of the cell storage device 1 for transplantation is transplanted into the subcutaneous tissue 102 immediately below the skin 101 in the transplantation target tissue 100 with the immune isolation membrane 14 side being the deep side of the subcutaneous tissue 102. Then, the tip 16 a of the step 16, which is higher than the upper surface of the housing 11 in FIG. 3 using the height of the step 16, is exposed outside the tissue 100 to which the living body is transplanted. Even when the cell storage device 1 for transplantation is transplanted into the subcutaneous tissue 102 directly below the skin 101, the height of the step 16 from the housing 11 may be 1 mm or more in consideration of the thickness of the human skin 101. desirable. The pipes 42 and 43 are connected to the introduction flow path 17 and the exhaust flow path 18 at the distal end 16a of the stepped portion 16 exposed to the outside of the living body transplantation destination tissue 100 with an adhesive or the like.

図4は、移植用細胞収容装置1を生体の移植先組織100内に移植した状態の他の例における縦断面図である。図4の例では、筐体11を生体の移植先組織100の深い位置に移植する例を示している。筐体11を生体の移植先組織100の深い位置に移植する分、段差部16の高さを図3の例よりも高くして段差部16の先端16aは生体の移植先組織100の外部に露出させている。   FIG. 4 is a vertical cross-sectional view of another example of a state where the cell storage device for transplantation 1 is transplanted into the transplantation target tissue 100 of a living body. The example of FIG. 4 shows an example in which the housing 11 is implanted at a deep position in the transplantation target tissue 100 of the living body. The height of the step 16 is made higher than that of the example in FIG. Exposed.

次に、本実施例の作用効果について説明する。
本実施例では、図3、図4に示すように、移植用細胞収容装置1の細胞室15内に所定の細胞111を収納してから筐体11に免疫隔離膜14を取り付ける。この移植用細胞収容装置1を前記の移植方法のように移植する。配管42,43は、移植前に移植用細胞収容装置1に接続してもよいし、移植後に接続してもよい。酸素供給装置31はポータブルな装置であり、人間の場合であれば腰部等に装着して使用する。これによって、配管42、導入流路17を介して酸素を含む空気が空洞部13内に供給される。そして、空気中の酸素が酸素透過膜12を介して細胞室15内の細胞111に供給される。
なお、移植先組織100における移植用細胞収容装置1の移植位置は、図4のような皮下組織102の深い部位とするよりも、図3のような皮下の位置であることが望ましい。皮下は手術が比較的容易で侵襲性も低いため、移植用細胞収容装置1の移植部位として好適だからである。
細胞111は所定の分泌物を分泌し、この分泌物は免疫隔離膜14を介して生体に供給される。例えば、膵島の細胞を細胞111として細胞室15内に収容し当該膵島が分泌するインスリンによって1型糖尿病を治療する等である。また、空洞部13内の排気は、排気流路18、配管43を介して外部に排出される。
Next, the operation and effect of this embodiment will be described.
In the present embodiment, as shown in FIGS. 3 and 4, predetermined cells 111 are stored in the cell chamber 15 of the cell storage device 1 for transplantation, and then the immune isolation membrane 14 is attached to the housing 11. The transplant cell storage device 1 is transplanted as in the above-described transplant method. The pipes 42 and 43 may be connected to the transplant cell storage device 1 before transplantation, or may be connected after transplantation. The oxygen supply device 31 is a portable device. In the case of a human, the oxygen supply device 31 is used by being attached to a waist or the like. Thereby, air containing oxygen is supplied into the cavity 13 through the pipe 42 and the introduction flow path 17. Then, oxygen in the air is supplied to the cells 111 in the cell chamber 15 via the oxygen permeable membrane 12.
It is desirable that the transplantation position of the cell storage device 1 for transplantation in the transplantation destination tissue 100 is a subcutaneous position as shown in FIG. 3 rather than a deep portion of the subcutaneous tissue 102 as shown in FIG. This is because the subcutaneous operation is relatively easy and the invasiveness is low, so that it is suitable as a transplant site of the cell storage device 1 for transplant.
The cells 111 secrete a predetermined secretion, and this secretion is supplied to the living body through the immune isolation membrane 14. For example, the cells of the pancreatic islets are accommodated in the cell chamber 15 as the cells 111, and the type 1 diabetes is treated with insulin secreted by the pancreatic islets. Further, the exhaust gas in the hollow portion 13 is exhausted to the outside via the exhaust passage 18 and the pipe 43.

本実施例では、移植用細胞収容装置1が段差部16を備えることによって、その先端16aを生体の移植先組織100の外部に露出させている。そのため、配管42,43と、導入流路17、排気流路18との接続部分は、生体の外部に露出している。もし、当該接続部分が生体の移植先組織100内に存在する場合は、生体が動くことで、その移植先組織100から当該接続部分は応力を受ける。このため、配管42,43と、導入流路17、排気流路18との接続部分ははずれ易くなる。これに対して、本実施例では、配管42,43と、導入流路17、排気流路18との接続部分は、生体の外部に露出しているため、当該接続部分は生体から応力を受けることがない。そのため、配管42,43と、導入流路17、排気流路18との接続部分が外れる可能性を低減することができる。   In this embodiment, the transplant cell storage device 1 includes the step portion 16 so that the distal end 16a is exposed to the outside of the living body transplantation destination tissue 100. Therefore, the connection portions between the pipes 42 and 43 and the introduction channel 17 and the exhaust channel 18 are exposed outside the living body. If the connection portion is present in the living body transplant destination tissue 100, the connection portion receives stress from the transplant destination tissue 100 as the living body moves. For this reason, the connection portions between the pipes 42 and 43 and the introduction flow path 17 and the exhaust flow path 18 are easily disconnected. On the other hand, in the present embodiment, since the connection between the pipes 42 and 43, the introduction flow path 17, and the exhaust flow path 18 is exposed to the outside of the living body, the connection is subjected to stress from the living body. There is no. Therefore, the possibility that the connection between the pipes 42 and 43 and the introduction flow path 17 and the exhaust flow path 18 is disconnected can be reduced.

また、皮膚101の直下の皮下組織102という最も移植先組織100の浅い位置に移植する場合でも、皮膚101の厚さ(人間の場合)を考慮すれば、段差部16の筐体11からの高さは1mm以上あることが望ましい。これによって、最も移植先組織100の浅い位置に移植する場合でも、段差部16の先端16aを皮膚101の外側に露出させることができる。
なお、本発明は上記した実施例に限定されるものではなく、様々な変形例が含まれる。例えば、上記した実施例は本発明を分かりやすく説明するために詳細に説明したものであり、必ずしも説明した全ての構成を備えるものに限定されるものではない。
Further, even in the case where the skin 101 is to be transplanted at the shallowest position of the subcutaneous tissue 102 immediately below the skin 101, the height of the step 16 from the housing 11 is considered in consideration of the thickness of the skin 101 (in the case of a human). It is desirable that the length is 1 mm or more. Thereby, even when transplanting to the shallowest position of the transplantation destination tissue 100, the tip 16a of the step 16 can be exposed outside the skin 101.
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.

例えば、空洞部13に導入するのは空気ではなく、酸素キャリアを含む液体などでもよい。
細胞111としては、例えばインスリン産生細胞、単離された膵島、間葉系幹細胞など、様々な細胞を用いることができる。
For example, what is introduced into the cavity 13 may be a liquid containing an oxygen carrier instead of air.
As the cells 111, various cells such as insulin-producing cells, isolated pancreatic islets, mesenchymal stem cells, and the like can be used.

[実験例]
3Dプリンタ(Stratasys製で、MED610インクを使用)を用いて製造した筐体11に、接着剤を用いて酸素透過膜12と免疫隔離膜14とを接着して移植用細胞収容装置1とした。段差部16の高さは1mmとした。

得られた移植用細胞収容装置1をマウス皮下に移植したところ、段差部16の先端16aは、マウスの皮膚よりも外側に露出する状態となることが確認された。 配管42から空気を1.6mL/minの流速で継続して通気することで酸素供給しながら経過観察した。1週間後の細胞111の生存率は60%と比較的高い値であった。
[Example of experiment]
The oxygen permeable membrane 12 and the immunoisolation membrane 14 were adhered to the housing 11 manufactured using a 3D printer (manufactured by Stratasys, using MED610 ink) using an adhesive to obtain the cell storage device 1 for transplantation. The height of the step 16 was 1 mm.

When the obtained cell storage device 1 for transplantation was transplanted under the skin of a mouse, it was confirmed that the tip 16a of the step 16 was exposed outside the skin of the mouse. The air was continuously supplied at a flow rate of 1.6 mL / min from the pipe 42 to observe the progress while supplying oxygen. One week later, the survival rate of the cells 111 was a relatively high value of 60%.

1 移植用細胞収容装置
11 筐体
11a 開口部
12 酸素透過膜
13 空洞部
14 免疫隔離膜
15 細胞室
16 段差部
16a 先端
17 導入流路
18 排気流路
31 酸素供給装置
42 配管
DESCRIPTION OF SYMBOLS 1 Cell storage device for transplantation 11 Housing 11a Opening 12 Oxygen permeable membrane 13 Cavity part 14 Immunoisolation membrane 15 Cell room 16 Step part 16a Tip 17 Introduction flow path 18 Exhaust flow path 31 Oxygen supply device 42 Pipe

Claims (3)

一方に開口部が形成された筐体と、
前記筐体の内部の空間を仕切って当該筐体内に空洞部を形成する酸素透過膜と、
前記酸素透過膜の前記空洞部側とは反対側で前記開口部を覆うように形成された免疫隔離膜と、
前記酸素透過膜と前記免疫隔離膜とによって囲まれた細胞室と、
前記筐体の前記免疫隔離膜側とは反対側の面に設けられ当該面よりも段差をなして高くなっている段差部と、
前記段差部の先端から前記空洞部までを貫く流路であり当該空洞部内に酸素を外部から供給する導入流路と、
前記段差部の先端から前記空洞部までを貫く流路であり当該空洞部内の排気を外部に排出する排気流路とを備え、
生体内に移植されることを特徴とする移植用細胞収容装置。
A housing having an opening formed on one side,
An oxygen permeable membrane that partitions the space inside the housing to form a cavity in the housing,
An immunoisolation membrane formed to cover the opening on the side opposite to the cavity side of the oxygen permeable membrane;
A cell chamber surrounded by the oxygen permeable membrane and the immune isolation membrane,
A step portion provided on a surface of the housing opposite to the immunoisolation membrane side and having a height higher than that surface,
An introduction flow path that is a flow path that penetrates from the tip of the step portion to the hollow portion and that supplies oxygen from the outside into the hollow portion,
An exhaust flow path that is a flow path that penetrates from the tip of the step portion to the hollow portion and that discharges exhaust gas in the hollow portion to the outside,
A cell storage device for transplantation, which is transplanted into a living body.
前記段差部は、高さが1mm以上あることを特徴とする請求項1に記載の移植用細胞収容装置。   The transplant cell storage device according to claim 1, wherein the height of the step portion is 1 mm or more. 請求項1又は請求項2に記載の移植用細胞収容装置と、
前記移植用細胞収容装置の前記導入流路と配管で接続され当該導入流路を介して前記空洞部に酸素を供給する酸素供給装置とを備えることを特徴とする移植用細胞収容システム。
A cell storage device for transplantation according to claim 1 or 2,
An oxygen supply device, comprising: an oxygen supply device connected to the introduction flow channel of the transplant cell storage device by a pipe and supplying oxygen to the cavity via the introduction flow channel.
JP2018133830A 2018-07-17 2018-07-17 Housing device of cells for transplantation, and housing system of cells for transplantation Pending JP2020010618A (en)

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PCT/JP2019/023372 WO2020017195A1 (en) 2018-07-17 2019-06-12 Cell storage device for implantation, cell storage system for implantation, and oxygen supply device

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