JP2000157623A - Cell carrier for transplanting cell - Google Patents
Cell carrier for transplanting cellInfo
- Publication number
- JP2000157623A JP2000157623A JP10337078A JP33707898A JP2000157623A JP 2000157623 A JP2000157623 A JP 2000157623A JP 10337078 A JP10337078 A JP 10337078A JP 33707898 A JP33707898 A JP 33707898A JP 2000157623 A JP2000157623 A JP 2000157623A
- Authority
- JP
- Japan
- Prior art keywords
- cell
- carrier
- micropores
- transplanted
- transplanted cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、移植細胞を臓器表
面に生着させるのに使用する細胞移植用細胞担体に関す
る。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cell carrier for cell transplantation used for engrafting transplanted cells on the surface of an organ.
【０００２】[0002]
【従来の技術】従来の細胞移植は、ドナーから採取した
細胞をレシピエントに移植する場合、その移植部位がレ
シピエントの臓器（肝臓、腎臓、血管、脳等）内部であ
る場合が多い。又、細胞を臓器表面に移植する場合は、
移植細胞を臓器表面にそのまま静置している。2. Description of the Related Art In conventional cell transplantation, when cells collected from a donor are transplanted to a recipient, the transplantation site is often inside a recipient organ (liver, kidney, blood vessel, brain, etc.). When transplanting cells to the surface of an organ,
The transplanted cells are left still on the organ surface.
【０００３】[0003]
【発明が解決しようとする課題】しかしながら、従来の
細胞移植では、臓器内部に細胞を移植する場合、正常に
機能する臓器（肝臓、腎臓、血管、脳等）に対して侵襲
的であり、危険を伴う。例えば、現在臨床で行われてい
る膵臓のランゲルハンス島（膵島）移植は門脈内移植が
主流であるが、門脈内移植では肝表面より肝臓内の血管
である門脈を穿刺し、且つ膵島を血管内に注入する点で
侵襲的である。又、膵島を注入する過程で細菌感染が生
じ、肝膿瘍といった合併症が発生する危険性がある。However, in the conventional cell transplantation, when cells are transplanted into an organ, it is invasive to a normally functioning organ (liver, kidney, blood vessel, brain, etc.), and it is dangerous. Accompanied by For example, transplantation of the pancreatic islets of Langerhans (pancreatic islets), which is currently performed in the clinic, is mainly performed by intraportal transplantation. Is invasive in that it is injected into blood vessels. In addition, there is a risk that bacterial infection may occur during the process of injecting the islets and complications such as liver abscess may occur.
【０００４】一方、臓器表面に細胞を移植する場合、移
植細胞が臓器表面からずれ易いために生着が困難であ
り、また目的部位に細胞を正確に移植し難い。従って、
本発明は、そのような問題点に着目してなされたもの
で、移植操作による合併症を併発することなく安全で確
実な細胞移植を実現できる手段を提供することを目的と
する。[0004] On the other hand, when cells are transplanted to the surface of an organ, engraftment is difficult because the transplanted cells are easily shifted from the surface of the organ, and it is difficult to transplant cells accurately to a target site. Therefore,
The present invention has been made in view of such a problem, and an object of the present invention is to provide means capable of realizing safe and reliable cell transplantation without complications caused by transplantation operation.
【０００５】[0005]
【課題を解決するための手段】前記目的は本発明の請求
項１、請求項３又は請求項５記載の細胞移植用細胞担体
により達成される。即ち、請求項１記載の細胞移植用細
胞担体は、移植細胞を臓器表面に生着させるのに使用す
る細胞担体であって、親水性で、表面に存在する微小孔
が移植細胞よりも小さいことを特徴とする。The above object is achieved by a cell carrier for cell transplantation according to claim 1, 3 or 5 of the present invention. That is, the cell carrier for cell transplantation according to claim 1 is a cell carrier used for engrafting the transplanted cells on the surface of the organ, and is hydrophilic and has small micropores present on the surface than the transplanted cells. It is characterized by.
【０００６】又、請求項３記載の細胞移植用細胞担体
は、移植細胞を臓器表面に生着させるのに使用する細胞
担体であって、親水性で、表面に存在する微小孔は移植
細胞よりも大きいと共に、当該微小孔に入った移植細胞
の表面が微小孔以外の担体表面とほぼ面一になる深さか
若しくはその深さよりも浅い深さを有することを特徴と
する。[0006] The cell carrier for cell transplant according to claim 3 is a cell carrier used for engrafting the transplanted cells on the surface of an organ, wherein the micropores which are hydrophilic and exist on the surface are smaller than those of the transplanted cells. And the surface of the transplanted cells entering the micropores has a depth that is almost flush with the surface of the carrier other than the micropores, or has a depth smaller than that depth.
【０００７】更に、請求項５記載の細胞移植用細胞担体
は、移植細胞を臓器表面に生着させるのに使用する細胞
担体であって、親水性の基体と、この基体上に少なくと
も部分的に移植細胞よりも小さい間隙を置いて設けられ
た多数条の凸部とからなることを特徴とする。これらの
細胞担体は、比較的安全な新しい細胞移植技術に係るも
のであり、移植細胞を含有する培養液を含浸させ、移植
細胞が付着した担体表面側をレシピエントの臓器表面に
載置することにより、移植細胞を臓器表面に移植するも
のである。Further, the cell carrier for cell transplant according to the fifth aspect is a cell carrier used for engrafting transplanted cells on the surface of an organ, comprising a hydrophilic substrate and at least a part on the substrate. It is characterized by comprising a number of convex portions provided with a smaller gap than the transplanted cells. These cell carriers are related to a relatively safe new cell transplantation technology, and are impregnated with a culture solution containing the transplanted cells, and the carrier surface to which the transplanted cells are attached is placed on the surface of the recipient organ. Thus, the transplanted cells are transplanted to the surface of the organ.
【０００８】請求項１記載の細胞担体では、表面の微小
孔が移植細胞よりも小さいので、移植細胞を含有する培
養液を含浸させると、培養液は微小孔を通じて担体内部
に吸収されるが、移植細胞は担体表面に残る。従って、
移植細胞が付着した担体表面側をレシピエントの臓器表
面に接触させて載置すれば、移植細胞は担体内部の培養
液で培養されつつ臓器表面に生着し、細胞の移植が行わ
れる。このため、移植細胞が臓器表面の目的部位からず
れたりすることがなく、安全且つ確実に細胞移植を行う
ことができる。しかも、移植操作は侵襲的ではなく、合
併症を併発することもない。In the cell carrier according to the first aspect, the micropores on the surface are smaller than the transplanted cells. Therefore, when the culture medium containing the transplanted cells is impregnated, the culture solution is absorbed into the carrier through the micropores. The transplanted cells remain on the carrier surface. Therefore,
When the surface of the carrier to which the transplanted cells are attached is placed in contact with the surface of the organ of the recipient, the transplanted cells are engrafted on the organ surface while being cultured in the culture solution inside the carrier, and the cells are transplanted. Therefore, the transplanted cells can be safely and reliably transplanted without being displaced from the target site on the organ surface. Moreover, the implantation procedure is not invasive and does not involve complications.
【０００９】請求項３記載の細胞担体では、微小孔は移
植細胞よりも大きいが、その微小孔の深さは微小孔に入
った移植細胞の表面が微小孔以外の担体表面とほぼ面一
になる深さか若しくはその深さよりも浅い深さであるた
め、移植細胞を含有する培養液を含浸させると、培養液
は微小孔を通じて担体内部に吸収される。移植細胞は微
小孔内に入るが、細胞表面は微小孔以外の担体表面とほ
ぼ面一になるか、若しくは担体表面よりも突出した状態
になる。従って、移植細胞が付着した担体表面側をレシ
ピエントの臓器表面に接触させて載置すれば、上記と同
様に細胞を臓器表面に移植することができる。In the cell carrier according to the third aspect, the micropores are larger than the transplanted cells, but the depth of the micropores is such that the surface of the transplanted cells entering the micropores is almost flush with the surface of the carrier other than the micropores. Since it is at a certain depth or shallower than that depth, when the culture solution containing the transplanted cells is impregnated, the culture solution is absorbed into the inside of the carrier through the micropores. The transplanted cells enter the micropores, but the cell surface is almost flush with the carrier surface other than the micropores, or protrudes from the carrier surface. Therefore, if the carrier surface to which the transplanted cells are attached is brought into contact with the organ surface of the recipient and placed, the cells can be transplanted to the organ surface in the same manner as described above.
【００１０】請求項５記載の細胞担体では、親水性の基
体上に設けられた多数条の凸部が少なくとも部分的に移
植細胞よりも小さい間隙を置いているので、移植細胞を
含有する培養液を含浸させると、培養液は基体内部に吸
収されるが、移植細胞は凸部に当たり、担体表面に残
る。従って、同様に移植細胞が付着した担体表面側をレ
シピエントの臓器表面に接触させて載置すれば、細胞を
移植できる。[0010] In the cell carrier according to the fifth aspect, since the multiple projections provided on the hydrophilic substrate at least partially have a gap smaller than that of the transplanted cell, the culture solution containing the transplanted cell is used. When the cell is impregnated, the culture solution is absorbed into the inside of the substrate, but the transplanted cells hit the projections and remain on the surface of the carrier. Therefore, the cells can be transplanted by placing the carrier surface to which the transplanted cells are adhered in contact with the organ surface of the recipient.
【００１１】請求項１記載の発明において、担体表面に
存在する微小孔は移植細胞よりも小さく、担体に培養液
を含浸させる際に移植細胞が担体内部に進入しなければ
十分である。具体的に微小孔の大きさは、最大移植細胞
に属する膵島の大きさの多くが１００μｍ以上であるこ
とから、微小孔のほぼ中央部における径が１００μｍ以
下である。因みに径が１００μｍよりも大きいと、生体
細胞はその平均的な大きさから微小孔を通じて担体内部
に入り込んでしまい、担体表面に残らない。In the first aspect of the invention, the micropores present on the surface of the carrier are smaller than the transplanted cells, and it is sufficient if the transplanted cells do not enter the inside of the carrier when the carrier is impregnated with the culture solution. More specifically, the size of the micropores is 100 μm or less at the approximate center of the micropores, since most of the islets belonging to the largest transplant cell are 100 μm or more. By the way, when the diameter is larger than 100 μm, the living cells enter the inside of the carrier through the micropores due to their average size and do not remain on the surface of the carrier.
【００１２】請求項３記載の発明において、担体表面に
存在する微小孔は、微小孔に入った移植細胞の表面が微
小孔以外の担体表面とほぼ面一になる深さか、若しくは
その深さよりも浅い深さであればよい。具体的に微小孔
の深さは、最大移植細胞に属する膵島の大きさの多くが
１００μｍ以上であることから、１００μｍ以下であ
る。因みに深さが１００μｍよりも深いと、細胞表面が
微小孔以外の担体表面よりも引っ込んだ状態になるの
で、担体を臓器表面に載置したときに移植細胞が臓器表
面に生着し難くなる。According to the third aspect of the present invention, the micropores present on the surface of the carrier have a depth such that the surface of the transplanted cells entering the micropores is substantially flush with the surface of the carrier other than the micropores, or is smaller than the depth. It is sufficient if the depth is shallow. Specifically, the depth of the micropores is 100 μm or less, since most of the islets belonging to the largest transplant cell are 100 μm or more. By the way, when the depth is more than 100 μm, the cell surface is in a state of being retracted from the surface of the carrier other than the micropores, so that when the carrier is placed on the surface of the organ, it becomes difficult for the transplanted cells to adhere to the surface of the organ.
【００１３】請求項５記載の発明において、凸部間の間
隙は少なくとも部分的に移植細胞よりも小さければよ
い。具体的に間隙は、前記したように生体細胞の平均的
大きさからすると１００μｍ以下である。因みに間隙が
１００μｍよりも大きいと、基体に存在する微小孔が移
植細胞よりも大きければ、移植細胞は間隙及び微小孔を
通じて基体内部に入り込んでしまう。この場合、間隙が
１００μｍ以下であれば、基体の微小孔の大きさを問わ
ずに移植細胞を担体表面に残すことができる。[0013] In the invention according to claim 5, the gap between the projections may be at least partially smaller than the transplanted cell. Specifically, the gap is 100 μm or less in terms of the average size of living cells as described above. Incidentally, if the gap is larger than 100 μm, if the micropores present in the substrate are larger than the transplanted cells, the transplanted cells will enter the inside of the substrate through the gaps and the micropores. In this case, if the gap is 100 μm or less, the transplanted cells can be left on the carrier surface regardless of the size of the micropores in the base.
【００１４】[0014]
【発明の実施の形態】以下、本発明を実施形態に基づい
て説明する。一実施形態に係る細胞移植用細胞担体の斜
視図を図１に示す。この細胞担体１は、生体に安全なも
のであれば、通常の担体に使用されている材料で構成さ
れるが、担体１自体がレシピエントの体内で移植細胞を
残して吸収される生体吸収性の場合には、コラーゲン、
ゼラチン、デンプン、フィブリン、血清アルブミン、ア
ルギン酸、キチン、キトサン、ヒアルロン酸、酸化セル
ロース等の材料が使用できる。但し、細胞担体１は必ず
しも吸収性である必要はなく、体内で吸収されずに細胞
移植後に取り除かれるものであってもよい。その場合の
生体非吸収性材料としては、セルロース、ポリビニルア
ルコール、ポリアクリル酸等が使用できる。DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described based on embodiments. FIG. 1 shows a perspective view of a cell carrier for cell transplantation according to one embodiment. The cell carrier 1 is composed of a material used for a normal carrier as long as it is safe for a living body, but the carrier 1 itself is absorbed in the recipient's body while leaving transplanted cells. In the case of collagen,
Materials such as gelatin, starch, fibrin, serum albumin, alginic acid, chitin, chitosan, hyaluronic acid, and oxidized cellulose can be used. However, the cell carrier 1 does not necessarily need to be absorbable, and may be removed after cell transplantation without being absorbed in the body. In that case, as the non-bioabsorbable material, cellulose, polyvinyl alcohol, polyacrylic acid, or the like can be used.
【００１５】このような材料からなる細胞担体１は、親
水性で、表面には無数の微小孔（隙間）２が存在するも
のである。図２に微小孔２を模式的に示すように、微小
孔２を円形と見なすと、微小孔２は移植細胞よりも小さ
く、具体的には微小孔２の孔径ｒは１００μｍ以下に設
定されている。因みに、孔径ｒが１００μｍよりも大き
いと、前記したように移植細胞が担体内部に進入し易く
なり、好ましくない。The cell carrier 1 made of such a material is hydrophilic and has numerous micropores (gap) 2 on its surface. As shown schematically in FIG. 2, when the micropores 2 are considered to be circular, the micropores 2 are smaller than the transplanted cells. Specifically, the pore diameter r of the micropores 2 is set to 100 μm or less. I have. Incidentally, when the pore diameter r is larger than 100 μm, the transplanted cells easily enter the inside of the carrier as described above, which is not preferable.
【００１６】なお、図１に示す細胞担体１は四角形状で
あり、寸法はａ×ｂ×ｔ＝５０ｍｍ×５０ｍｍ×１ｍｍ
であるが、この形状やサイズは一例であり、適宜変更す
ればよい。細胞移植の際には、上記のような細胞担体１
に移植細胞を播種するために、移植細胞を含有する培養
液を細胞担体１に含浸させる。すると、図３の部分拡大
断面図に示すように、細胞担体１は親水性であるから、
培養液は微小孔２を通じて担体１内部に吸収されるが、
微小孔２は移植細胞１０より小さいから、移植細胞１０
は担体１表面に付着した状態になる。そして、図４に示
すように、移植細胞１０が付着した担体１表面側をレシ
ピエントの臓器表面に接触させて載置することにより、
移植細胞１０を臓器２０の表面に移植する。The cell carrier 1 shown in FIG. 1 has a rectangular shape, and has dimensions a × b × t = 50 mm × 50 mm × 1 mm.
However, these shapes and sizes are merely examples, and may be changed as appropriate. At the time of cell transplantation, the cell carrier 1 as described above is used.
The cell carrier 1 is impregnated with a culture solution containing the transplanted cells in order to inoculate the cells with the transplanted cells. Then, as shown in the partially enlarged sectional view of FIG. 3, the cell carrier 1 is hydrophilic,
The culture solution is absorbed into the carrier 1 through the micropores 2,
Since the micropores 2 are smaller than the transplant cells 10, the transplant cells 10
Is attached to the surface of the carrier 1. Then, as shown in FIG. 4, by placing the surface of the carrier 1 to which the transplanted cells 10 are attached in contact with the surface of the organ of the recipient,
The transplant cell 10 is transplanted on the surface of the organ 20.
【００１７】上記実施形態では、微小孔２は円形とみな
したが、円形以外にも、図５に示すような形状であって
もよい。図５の（ａ）には楕円形の微小孔２ａを、図５
の（ｂ）にはほぼ瓢箪形の微小孔２ｂを、図５の（ｃ）
にはほぼ三角形の微小孔２ｃを、図５の（ｄ）にはほぼ
四角形の微小孔２ｄを示してある。いずれの微小孔２
（ａ〜ｄ）も、そのほぼ中央部における径ｄ（１〜４）
が１００μｍ以下であり、移植細胞は微小孔２（ａ〜
ｄ）内に入り込まない。In the above embodiment, the micro holes 2 are regarded as circular, but may have a shape other than the circular shape as shown in FIG. FIG. 5A shows an elliptical micro hole 2a, and FIG.
(B) shows a roughly gourd-shaped micropore 2b, and (c) of FIG.
5A shows a substantially triangular micropore 2c, and FIG. 5D shows a substantially square micropore 2d. Any micro holes 2
(A to d) also have a diameter d (1 to 4) at a substantially central portion thereof.
Is 100 μm or less, and the transplanted cells have micropores 2 (a to
d) Do not get inside.
【００１８】別実施形態に係る細胞移植用細胞担体の部
分拡大断面図を図６に示す。図６の（ａ）の細胞担体１
では、微小孔２ｅは円形や図５に示すような形状であ
り、移植細胞１０よりも大きいと共に、微小孔２ｅに入
った移植細胞１０の表面が微小孔２ｅ以外の担体１表面
とほぼ面一になる深さか若しくはその深さよりも浅い深
さを有する。微小孔２ｅの具体的な大きさとしては、微
小孔２ｅのほぼ中央部における径ｄ５は１００μｍより
も大きく、微小孔２ｅの深さｈは１００μｍ以下であ
る。FIG. 6 is a partially enlarged sectional view of a cell carrier for cell transplantation according to another embodiment. Cell carrier 1 in FIG.
5, the micropore 2e is circular or shaped as shown in FIG. 5, is larger than the transplant cell 10, and the surface of the transplant cell 10 entering the micropore 2e is almost flush with the surface of the carrier 1 other than the micropore 2e. Or shallower than that depth. As the specific size of the micropores 2e, the diameter d5 at the approximate center of the micropores 2e is larger than 100 μm, and the depth h of the micropores 2e is 100 μm or less.
【００１９】この細胞担体１に移植細胞を含有する培養
液を含浸させると、培養液は担体１内部に吸収され、移
植細胞１０は微小孔２ｅに入る。しかし、移植細胞１０
の表面は微小孔２ｅ以外の担体１表面とほぼ面一になる
か、若しくは担体１表面よりも突出した状態になる。従
って、前記と同様に、移植細胞１０が付着した担体１表
面側を臓器表面に接触させて載置することにより、移植
細胞１０を臓器２０の表面に移植することができる。When the cell carrier 1 is impregnated with a culture solution containing transplant cells, the culture solution is absorbed into the carrier 1 and the transplant cells 10 enter the micropores 2e. However, transplanted cells 10
Is almost flush with the surface of the carrier 1 other than the micropores 2e, or protrudes from the surface of the carrier 1. Therefore, similarly to the above, the transplant cell 10 can be transplanted on the surface of the organ 20 by placing the surface of the carrier 1 to which the transplant cell 10 has adhered in contact with the organ surface.
【００２０】又、図６の（ｂ）では、微小孔２ｆの底面
が波状になっている場合で、図６の（ｃ）では、１つの
微小孔２ｇに複数（ここでは２つ）の移植細胞１０が入
っている場合である。いずれも、前記と同等の作用効果
が得られる。更に別実施形態に係る細胞移植用細胞担体
の斜視図を図７の（ａ）に、その部分拡大断面図を図７
の（ｂ）に示す。この細胞担体１は、親水性の基体５
と、この基体５上に少なくとも部分的に移植細胞１０よ
りも小さい間隙７を置いて設けられた多数条の凸部６と
からなる。間隙７は、具体的には１００μｍ以下であ
る。但し、間隙７は、全ての部分において１００μｍ以
下である必要はなく、部分的に１００μｍ以下であれば
よい。又、凸部６は、例えば糸であり、また親水性であ
る必要はなく、疎水性材料からなってもよい。FIG. 6 (b) shows a case where the bottom surface of the minute hole 2f is wavy. In FIG. 6 (c), a plurality (two in this case) of transplants are placed in one minute hole 2g. This is the case where the cells 10 are contained. In each case, the same operation and effect as described above can be obtained. FIG. 7A is a perspective view of a cell carrier for cell transplantation according to still another embodiment, and FIG.
(B) of FIG. This cell carrier 1 comprises a hydrophilic substrate 5
And a plurality of convex portions 6 provided at least partially on the base 5 with a gap 7 smaller than the transplanted cells 10. The gap 7 is specifically 100 μm or less. However, the gap 7 does not need to be 100 μm or less in all parts, but may be 100 μm or less in some parts. The protrusion 6 is, for example, a thread, and need not be hydrophilic, and may be made of a hydrophobic material.
【００２１】この細胞担体１に移植細胞を含有する培養
液を含浸させると、培養液は基体５内部に吸収される
が、移植細胞１０は凸部６に当たり、間隙７に入り込ま
ない。従って、移植細胞１０が付着した担体１表面側を
臓器表面に接触させて載置すれば、移植細胞１０を臓器
２０の表面に移植できる。又、この場合、移植細胞１０
が凸部６に当たり、基体５内部に進入しないので、基体
５の表面に存在する微小孔（図示せず）は移植細胞１０
より大きくてもよく、微小孔の大きさを問題とせずに細
胞移植を行うことができる。When the cell carrier 1 is impregnated with a culture solution containing transplanted cells, the culture solution is absorbed into the inside of the base 5, but the transplanted cells 10 hit the projections 6 and do not enter the gap 7. Therefore, if the surface of the carrier 1 to which the transplant cells 10 are adhered is placed in contact with the organ surface, the transplant cells 10 can be transplanted to the surface of the organ 20. In this case, the transplanted cells 10
Strikes the convex portion 6 and does not enter the inside of the base 5, so that micropores (not shown) existing on the surface of the base 5
It may be larger, and cell transplantation can be performed without considering the size of the micropore.
【００２２】なお、凸部６は直線状である必要はなく、
図８の（ａ）のような屈曲線状の凸部６ａや、図８の
（ｂ）のような湾曲線状の凸部６ｂでも構わず、いずれ
も前記と同等の作用効果が得られる。上記各実施形態に
示す細胞担体１では、いずれも細胞担体１に培養液を含
浸させて直ぐに細胞移植を行う必要はなく、細胞担体１
に移植細胞を播種し、数日培養した後に細胞移植を行う
ことも可能である。 ＜実験例＞次に、上記のような細胞担体１を用いた細胞
移植の実験例について説明する。 （使用動物と方法）ドナーには雄性ＡＣＩラット（体重
２００〜２２０ｇ）を用い、レシピエントにはストレプ
トゾトシン６０ｍｇ／ｋｇの静脈内注射による投与によ
り糖尿病を作製した雄性同系ＡＣＩラット（体重１９０
〜２５０ｇ）を用いた。The projection 6 does not need to be linear.
A bent linear convex portion 6a as shown in FIG. 8A or a curved linear convex portion 6b as shown in FIG. 8B may be used, and the same operation and effect as above can be obtained. In the cell carrier 1 shown in each of the above embodiments, it is not necessary to immediately carry out cell transplantation by impregnating the cell carrier 1 with the culture solution.
It is also possible to inoculate the cell with the transplanted cell and culture it for several days before performing cell transplantation. <Experimental Example> Next, an experimental example of cell transplantation using the above-described cell carrier 1 will be described. (Animals and Methods Used) Male ACI rats (body weight: 200-220 g) were used as donors, and male syngeneic ACI rats (body weight: 190 mg) having diabetes produced by intravenous injection of 60 mg / kg of streptozotocin were used as recipients.
２５０250 g).
【００２３】まず、ドナーより膵臓を摘出して、コラゲ
ナーゼ消化法及びデキストラン不連続濃度勾配法により
ランゲルハンス島（膵島）を分離・精製した。この膵島
２０００個を細胞担体１に播種し、細胞担体１の膵島付
着面をレシピエントの肝臓表面に接触させて載置するこ
とにより、膵島を移植した。移植後、レシピエント（６
匹）の非空腹時の血糖値と体重をそれぞれ６日目、１６
日目、２４日目、５０日目、９０日目に測定し、移植後
１４０日目にレシピエントを犠死させ、移植膵島の組織
学的検討を行った。 （結果）図９の表に示すように、血糖値は移植前値５０
７±６２ｍｇ／ｄｌから徐々に低下し、３週間以内に全
て２００ｍｇ／ｄｌ以下の低値（正常値）となり、有意
の低値を持続した。体重は移植前は減少していたが、移
植後増加した。又、合併症は認められなかった。組織学
的検討では、Ｈ．Ｅ．染色、インスリン染色により移植
膵島の生存を確認した。但し、図９の表において、ｐ＜
０．０５は移植前値より統計学的に有意に差があること
を表す。 （結論）細胞担体１を用いた肝臓表面への新しい膵島の
移植により、移植膵島は良好な機能を示し、移植操作に
よる合併症を併発せず、安全な細胞移植技術であること
が分かる。First, the pancreas was excised from the donor, and the islets of Langerhans (islets) were separated and purified by the collagenase digestion method and the dextran discontinuous concentration gradient method. 2000 pancreatic islets were seeded on the cell carrier 1, and the islet-adhering surface of the cell carrier 1 was placed in contact with the liver surface of the recipient, whereby the islets were transplanted. After transplantation, the recipient (6
Non-fasting blood glucose level and body weight on day 6 and 16 respectively.
The measurement was performed on days 24, 50, and 90, and the recipient was sacrificed 140 days after transplantation, and histological examination of the transplanted islets was performed. (Results) As shown in the table of FIG.
It gradually decreased from 7 ± 62 mg / dl, and all became low values (normal values) of 200 mg / dl or less within three weeks, and remained significantly low. Body weight had decreased before transplantation but increased after transplantation. No complications were observed. In histological examination, H. et al. E. FIG. The survival of the transplanted islets was confirmed by staining and insulin staining. However, in the table of FIG.
0.05 indicates that there is a statistically significant difference from the value before transplantation. (Conclusion) The transplantation of new islets to the liver surface using the cell carrier 1 shows that the transplanted islets show a good function, do not cause complications due to the transplantation operation, and are a safe cell transplantation technique.
【００２４】[0024]
【発明の効果】以上説明したように、本発明の請求項
１，３，５記載の細胞移植用細胞担体によれば、移植操
作による合併症を併発することなく安全で確実な細胞移
植を実現できる。As described above, according to the cell carrier for cell transplantation according to the first, third, and fifth aspects of the present invention, safe and reliable cell transplantation can be realized without complications caused by the transplantation operation. it can.
【図１】一実施形態に係る細胞移植用細胞担体の斜視図
である。FIG. 1 is a perspective view of a cell carrier for cell transplantation according to one embodiment.
【図２】図１の細胞担体における表面の微小孔を模式的
に示す平面図である。FIG. 2 is a plan view schematically showing micropores on the surface of the cell carrier of FIG.
【図３】図１の細胞担体に移植細胞を含有する培養液を
含浸させたときの部分拡大断面図である。FIG. 3 is a partially enlarged cross-sectional view when the cell carrier of FIG. 1 is impregnated with a culture solution containing transplanted cells.
【図４】培養液を含浸させた細胞担体を臓器表面に接触
させて載置した状態を示す断面図である。FIG. 4 is a cross-sectional view showing a state where a cell carrier impregnated with a culture solution is placed in contact with the organ surface.
【図５】図１の細胞担体における微小孔の各種形状変更
例を示す図である。FIG. 5 is a view showing examples of various shapes of micropores in the cell carrier of FIG. 1;
【図６】別実施形態に係る細胞移植用細胞担体の部分拡
大断面図（ａ）、同細胞担体における微小孔の形状変更
例を示す部分拡大断面図（ｂ）、及び同細胞担体におけ
る微小孔の別の形状変更例を示す部分拡大断面図（ｃ）
である。FIG. 6 is a partially enlarged cross-sectional view of a cell carrier for cell transplantation according to another embodiment (a), a partially enlarged cross-sectional view showing an example of changing the shape of micropores in the cell carrier, and micropores in the cell carrier. Partial enlarged cross-sectional view showing another example of the shape change of FIG.
It is.
【図７】更に別実施形態に係る細胞移植用細胞担体の斜
視図（ａ）、及び同細胞担体の部分拡大断面図（ｂ）で
ある。FIG. 7 is a perspective view (a) of a cell carrier for cell transplantation according to still another embodiment, and a partially enlarged cross-sectional view (b) of the cell carrier.
【図８】図７の細胞担体における凸部の形状変更例を示
す平面図（ａ）、及び同細胞担体における凸部の別の形
状変更例を示す平面図（ｂ）である。8A is a plan view illustrating an example of a change in the shape of a convex portion in the cell carrier of FIG. 7, and FIG. 8B is a plan view illustrating another example of a change in the shape of the convex portion in the cell carrier.
【図９】実験例の結果（移植後日数・非空腹時血糖値）
を示す表である。FIG. 9: Results of experimental examples (days after transplantation / non-fasting blood glucose level)
FIG.
１ 細胞担体 ２（ａ〜ｇ） 微小孔 ５ 基体 ６（ａ，ｂ） 凸部 ７ 間隙 １０ 移植細胞 ２０ 臓器 DESCRIPTION OF SYMBOLS 1 Cell carrier 2 (ag) Micropore 5 Substrate 6 (a, b) Convex part 7 Gap 10 Transplanted cell 20 Organ
───────────────────────────────────────────────────── フロントページの続き Ｆターム(参考） 4B033 NA01 NA16 NB56 NB63 NB68 NC04 NC14 ND12 4B065 AA90X BC41 CA44 4C081 AA14 AC16 BA03 BA12 CA051 CA081 CD021 CD031 CD081 CD091 CD121 CD151 CD171 DA04 DA05 DB06 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4B033 NA01 NA16 NB56 NB63 NB68 NC04 NC14 ND12 4B065 AA90X BC41 CA44 4C081 AA14 AC16 BA03 BA12 CA051 CA081 CD021 CD031 CD081 CD091 CD121 CD151 CD171 DA04 DA05 DB06
Claims (6)
する細胞担体であって、親水性で、表面に存在する微小
孔は移植細胞よりも小さいことを特徴とする細胞移植用
細胞担体。1. A cell carrier used for engrafting transplanted cells on the surface of an organ, wherein the cell carrier is hydrophilic and has micropores present on the surface smaller than the transplanted cells. .
おける径が１００μｍ以下であることを特徴とする請求
項１記載の細胞移植用細胞担体。2. The cell carrier for cell transplantation according to claim 1, wherein said micropores have a diameter at a substantially central portion of said micropores of 100 μm or less.
する細胞担体であって、親水性で、表面に存在する微小
孔は移植細胞よりも大きいと共に、当該微小孔に入った
移植細胞の表面が微小孔以外の担体表面とほぼ面一にな
る深さか若しくはその深さよりも浅い深さを有すること
を特徴とする細胞移植用細胞担体。3. A cell carrier used for engrafting transplanted cells on the surface of an organ, said cell carrier being hydrophilic and having micropores present on the surface larger than the transplanted cells and having the micropores in said micropores. A cell carrier for cell transplantation, characterized in that the surface has a depth substantially equal to or less than the surface of the carrier other than the micropores.
であることを特徴とする請求項３記載の細胞移植用細胞
担体。4. The cell carrier according to claim 3, wherein said micropores have a depth of 100 μm or less.
する細胞担体であって、親水性の基体と、この基体上に
少なくとも部分的に移植細胞よりも小さい間隙を置いて
設けられた多数条の凸部とからなることを特徴とする細
胞移植用細胞担体。5. A cell carrier used for engrafting transplanted cells on the surface of an organ, comprising: a hydrophilic substrate; and a space provided on the substrate at least partially with a smaller gap than the transplanted cells. A cell carrier for cell transplantation, comprising a plurality of convex portions.
特徴とする請求項５記載の細胞移植用細胞担体。6. The cell carrier according to claim 5, wherein the gap is 100 μm or less.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33707898A JP4437201B2 (en) | 1998-11-27 | 1998-11-27 | Cell carrier for cell transplantation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33707898A JP4437201B2 (en) | 1998-11-27 | 1998-11-27 | Cell carrier for cell transplantation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000157623A true JP2000157623A (en) | 2000-06-13 |
| JP4437201B2 JP4437201B2 (en) | 2010-03-24 |
Family
ID=18305237
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP33707898A Expired - Lifetime JP4437201B2 (en) | 1998-11-27 | 1998-11-27 | Cell carrier for cell transplantation |
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| Country | Link |
|---|---|
| JP (1) | JP4437201B2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004101736A1 (en) * | 2003-05-15 | 2004-11-25 | Phytoculture Control Co., Ltd. | Apparatus for culturing organism and culture method |
| JP2005529598A (en) * | 2002-06-11 | 2005-10-06 | セルトリックス・エービー | Porous gelatin material, gelatin structure, preparation method thereof and use thereof |
| JP2008148685A (en) * | 2006-11-21 | 2008-07-03 | Covalent Materials Corp | Carrier for culturing undifferentiated cell, and subculture method |
| US9096826B2 (en) | 2005-11-22 | 2015-08-04 | Covalent Materials Corporation | Culture substrate and culture method for undifferentiated cell and undifferentiated cultured cell |
| US9428728B2 (en) | 2006-11-21 | 2016-08-30 | Coorstek Kk | Carrier for undifferentiated cell culture and subculture method thereof |
-
1998
- 1998-11-27 JP JP33707898A patent/JP4437201B2/en not_active Expired - Lifetime
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005529598A (en) * | 2002-06-11 | 2005-10-06 | セルトリックス・エービー | Porous gelatin material, gelatin structure, preparation method thereof and use thereof |
| WO2004101736A1 (en) * | 2003-05-15 | 2004-11-25 | Phytoculture Control Co., Ltd. | Apparatus for culturing organism and culture method |
| US9096826B2 (en) | 2005-11-22 | 2015-08-04 | Covalent Materials Corporation | Culture substrate and culture method for undifferentiated cell and undifferentiated cultured cell |
| JP2008148685A (en) * | 2006-11-21 | 2008-07-03 | Covalent Materials Corp | Carrier for culturing undifferentiated cell, and subculture method |
| US9428728B2 (en) | 2006-11-21 | 2016-08-30 | Coorstek Kk | Carrier for undifferentiated cell culture and subculture method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4437201B2 (en) | 2010-03-24 |
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