JP2001299908A - Cell transplantation bag and artificial pancreas - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a cell transplantation bag capable of inducing a blood vessel new formation and an artificial pancreas using it. SOLUTION: This cell transplantation bag comprises a permeable bag formed of a polymer material and a gradually releasable carrier containing collagen and a blood vessel new formation-inducing factor, the carrier being housed in the bag. The blood vessel new formation is promoted by the synergism of the both, and the function of a transplanted cell can be kept over a long period. This artificial pancreas is formed by transplanting a pancreatic islet into the cell transplantation bag, and it is usable for a long period since the function of the pancreatic islet can be kept over a long period by the above effect.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a cell transplant bag and an artificial pancreas using the same. More specifically, while securing a space for cell transplantation, a cell transplantation bag capable of forming a capillary bed necessary for supplying oxygen and nutrients to transplanted cells from tissues around the space, The present invention relates to an artificial pancreas suitably used for treatment of insulin-dependent diabetes mellitus (IDDM, diabetes type I).

[0002]

2. Description of the Related Art In general, diabetes is one of the causes of death due to illness, which is one of extremely high mortality rates, and leg amputation is not caused by blindness, kidney disease, nervous imbalance, cardiovascular disease or accident. It is also the cause. In Japan, insulin preparations are currently mainly used for the treatment of diabetes type I. That is, a method of administering a required amount of an insulin preparation according to the blood glucose concentration of a patient measured in advance has been used.
However, since it is not possible to administer insulin at any time according to a continuous change in the blood glucose concentration of the patient, it is not possible to physiologically control the glucose metabolism of the patient. Therefore, it is difficult to prevent complications of diabetes such as vascular disorders and kidney disorders.

Accordingly, Japanese Patent Application Laid-Open No. 5-1 has been proposed as a new therapeutic method.
Hybrid artificial pancreas utilizing a biofeedback system as disclosed in Japanese Patent No. 54195 has attracted attention. The hybrid artificial pancreas is a tissue that secretes insulin, that is, a pancreatic islet of Langerhans (hereinafter abbreviated as islet of pancreatic islet), which is encapsulated and immobilized in a semipermeable membrane to isolate it from the patient's defense system (immune system, etc.). , For transplantation. Also, as disclosed in Japanese Patent Publication No. Hei 8-504625, in the United States, diabetes is one of the very high causes of mortality due to illness. There are only diseases and neonatal diseases, and treatment methods such as daily administration of insulin preparations have been improved as in Japan. Nevertheless, the majority of insulin-dependent diabetics are unable to maintain the long-term control of blood glucose necessary to avoid complications. In the United States, various approaches have been taken to find an alternative to daily insulin administration to treat type I diabetes, and research is being done to achieve steady blood glucose levels. The basic idea is to design a biofeedback system that releases insulin in response to blood glucose concentration, as described above, and at least three approaches have been studied. The first is a computer-controlled insulin pump with a glucose sensor implanted in the body, the second is a glycosylated insulin-conjugated concanavalin A system, and the third is an immune membrane with an artificial membrane. Microencapsulation using protected islets or artificial pancreas and other endocrine glands using semipermeable membranes, which are disclosed in US Pat. No. 4,323,457.
No. 4,391,909; U.S. Pat.
No. 378,016.

[0004] Among them, the artificial pancreas is disclosed in Tokuheihei 1
As disclosed in Japanese Patent Application Laid-Open No. 1-508777, living pancreatic endocrine cells of a heterologous living body are transplanted into a living body to function, and the transplanted pancreatic endocrine cells are rejected by the living body. It is protected with certain materials that protect it from reaction and maintain its function. Artificial pancreas has been considered as an artificial pancreas installed in the circulation route (hybrid artificial pancreas) or an artificial pancreas installed in the abdominal cavity depending on the transplantation site. Inhibition of growth of endocrine cells and deterioration of pancreatic endocrine cells are problems, and they have not been endurable for long-term use. One of the artificial pancreas installed in the abdominal cavity is a diffusion chamber type
There is an artificial pancreas. In this method, pancreatic endocrine cells are encapsulated by a polymer protective membrane or a support membrane that allows insulin and glucose to permeate. By implanting this diffusion chamber type artificial pancreas in diabetic patients, it is said that the required amount of insulin required for the treatment of diabetes can be reduced for several months. Also, various materials have been studied as materials for enclosing pancreatic islets in a hybrid artificial pancreas. For example, Sun et al. Entrap and immobilize pancreatic islets with a material consisting of a three-layered structure of an alginate-polylysine-alginate polyion complex (GM
O'SHEA and AM Sun, DIABETES, 35 , 943, 1986). On the other hand, Iwata et al. Have comprehensively immobilized pancreatic islets with agarose and agarose degradation products (Hirio Iwata, Hiroshi Amemiya, Takehisa Matsuda, Ryosuke Hayashi, Hisaki Takano, Tetsuzo Akutsu, Artificial Organs, 1)
6,1263 (1987) and JP-A-62-21553.
No. 0).

[0005]

As described above, when transplanting cells that secrete hormones such as insulin in an artificial pancreas or the like, insulin is carried to the site of action by the bloodstream, so that the site of transplantation of cells is There were not many restrictions. However, transplanted cells cannot survive without a sufficient supply of oxygen and nutrients, and the scavenging of oxygen at sites with many capillaries, such as under the capsule of the kidney, in the liver and spleen, or between transplanted cells. In order to eliminate this, the inside of the abdominal cavity or the like where a large area can be secured has been used as a cell transplant site. However, in such transplantation, there are problems that a large amount of cells cannot be transplanted and that a large operation for transplantation into a deep part in the body is required due to the limited site that can be used for transplantation. . Further, when the transplanted cells adversely affect the patient, it is necessary to remove the transplanted cells, but a major operation was also required to remove the cells transplanted deep into the body. Furthermore, when transplanted cells lose their function or function is deteriorated, it is necessary to refill them with new cells.However, when transplanted into a deep part of the body, refilling of cells cannot be performed easily. There was a problem.

The inventors of the present invention have conducted intensive studies to solve these problems, and as a result, have found that a subcutaneous or intramuscular place is preferred as a place for cell transplantation. In other words, a subcutaneous or intramuscular transplant can be performed by a simple operation, and the transplanted cells can be easily refilled. However, it was found that when transplanted subcutaneously or intramuscularly, the capillaries that supply oxygen and nutrients to the transplanted cells are not densely located near the transplanted cells. did. From such a problem, the present inventors have studied an artificial pancreas capable of generating capillaries capable of supplying oxygen and nutrients to transplanted cells. That is, the inventors of the present invention have proposed polyethylene terephthalate (P) encapsulating gelatin microspheres impregnated with basic fibroblast growth factor (bFGF).
ET) An artificial pancreas was prepared by embedding a mesh bag under the back of the animal, and then transplanting allogeneic pancreatic islets into the bag, and examined the effect. However, as will be described in detail in Examples below, in such a method, the angiogenesis ability of sustained-release bFGF was not sufficient in a diabetic model animal, and the function of the transplanted cells could not be sufficiently exhibited. Based on these findings, the present inventors have further studied and found that a bag obtained by simultaneously encapsulating collagen (eg, collagen sponge) and gelatin microspheres impregnated with bFGF in a PET mesh bag is implanted subcutaneously. It was found that angiogenesis was significantly increased, and that the function of the transplanted cells could be satisfactorily expressed. The present invention is based on such findings, and an object of the present invention is to provide a tool capable of promoting angiogenesis, forming and controlling an appropriate cell transplant site, and an artificial pancreas using the same.

[0007]

Means for Solving the Problems The gist of the present invention made in order to solve the above-mentioned problems is that a sustained-release carrier containing collagen and an angiogenesis-inducing factor is placed in a permeable bag made of a polymer material. This is a cell transplantation bag that is housed. In the above bag for cell transplantation,
The angiogenesis-inducing factor is preferably basic fibroblast growth factor (bFGF), the sustained-release carrier is preferably gelatin microspheres, and the collagen is preferably collagen sponge. It is preferably used for Also,
The artificial pancreas of the present invention comprises islets transplanted into the above-mentioned cell transplant bag, and it is preferable to use allogeneic islets as the pancreatic islets.

[0008]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS As described above, the cell transplantation bag of the present invention is obtained by accommodating a sustained release carrier containing collagen and an angiogenesis-inducing factor in a permeable bag made of a polymer material. Become. As the polymer material, any material can be used as long as it has biocompatibility. For example, PET, derivatives such as cellulose and cellulose acetate, polyvinyl alcohol and its derivatives, polysulfone, polycarbonate, tetra Examples thereof include fluoroethylene, vinylidene fluoride, and vinyl chloride-acrylonitrile copolymer. In the present invention, regardless of the name, the bag may be in any form (container) capable of storing a sustained release carrier containing collagen and an angiogenesis-inducing factor, and examples thereof include a bag shape and a tube shape. .

The bag for cell transplantation of the present invention is permeable, and the angiogenesis-inducing factor released from the sustained-release carrier in the bag and the insulin produced by the islets in the artificial pancreas described below are transferred to the outside of the bag. It is possible to move to. In addition, in order to prevent cells from entering the bag from the outside and proliferating, the bag preferably has a pore size that does not allow cells to pass through from the outside. That is, the angiogenesis-inducing factor and insulin can move out of the bag, while oxygen and nutrients can move into the bag, allowing the transplanted pancreatic islet cells to grow, while preventing the cells from entering the bag. In addition, it is possible to promote the growth and expression of functions of the transplanted cells in the bag. Examples of the form of the bag having such a permeability include a mesh shape and a porous membrane (semi-permeable membrane). Further, the film may be a single layer film, a laminated film, a coating film, or the like.

The sustained-release carrier in the present invention is not particularly limited as long as it can contain an angiogenesis-inducing factor. Examples of the sustained-release carrier include a living body comprising proteins such as gelatin and collagen, and polysaccharides such as hyaluronic acid and alginic acid. Absorbable hydrogels are preferred. As a method for producing such a hydrogel, a known crosslinking method using chemistry, heat, ultraviolet light, or the like can be used. Although the absorbability of the hydrogel is not particularly limited, it is preferable that the hydrogel be absorbed after the induction of angiogenesis so as not to interfere. The shape of the hydrogel is also not particularly limited, and may be any shape such as a film, a sheet, a tube, a rod, a microsphere, and a paste. The microsphere shape is preferred from the viewpoint of easy handling.

The above-mentioned sustained-release carrier contains an angiogenesis-inducing factor. The angiogenesis-inducing factor is not particularly limited as long as it can induce angiogenesis. For example, vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor ( aFG
F), platelet-derived growth factor, transforming growth factor-β (TGF-β), osteonectin (Osteonect)
in), angiopoietin, hepatocyte growth factor (HGF)
And the like. The sustained-release carrier containing such an angiogenesis-inducing factor can be prepared by a conventional method such as impregnating the sustained-release carrier with the angiogenesis-inducing factor.
Further, the amount of the angiogenesis-inducing factor contained in the sustained-release carrier can be appropriately adjusted depending on the desired angiogenesis.

In the present invention, collagen is used together with a sustained-release carrier containing the above-mentioned angiogenesis-inducing factor. For collagen used, collagen extraction method,
The type, site, age, collagen type, etc. of the animal are not particularly limited, but it is preferable to use type I. In addition, the biodegradability of collagen is affected by its production method and cross-linking method, but the angiogenesis-inducing effect of the present invention is recognized regardless of its degradability. The shape of the collagen contained in the bag is not particularly limited, and may be, for example, spongy, fibrous, granular or the like, and it is preferable to use a collagen sponge. The shape of the collagen sponge is not particularly limited, and examples thereof include shapes of films, sheets, rods, particles, pastes, and the like. As a method for producing a collagen sponge, various known production methods and cross-linking methods can be used. In addition, in the above collagen,
If necessary, polysaccharides such as hyaluronic acid and heparan sulfate, extracellular matrix components and the like may be added.

The bag for cell transplantation of the present invention contains a sustained-release carrier containing collagen and an angiogenesis-inducing factor in the above-described bag, and the form is not particularly limited as long as it contains these. It is preferable that a collagen sponge and a sustained-release carrier containing an angiogenesis-inducing factor are uniformly dispersed and enclosed in a bag. The ratio of the collagen and the sustained release carrier containing the angiogenesis inducing factor contained in the bag can be appropriately adjusted depending on the transplantation site, the content of the angiogenesis inducing factor in the sustained release carrier, and the like.
The collagen is used in an amount of about 0.1 to 50 parts by weight, preferably about 0.5 to 20 parts by weight, more preferably about 1 to 10 parts by weight, based on 1 part by weight of the sustained release carrier containing the angiogenesis-inducing factor. Is less than 0.1 part by weight, the induction of angiogenesis is insufficient, and if it exceeds 50 parts by weight, the capacity of the sustained release carrier may decrease.

FIG. 1 is a conceptual view of a cut end face at the center of an example of the cell transplant bag of the present invention. In the figure, 1 is PET
Mesh bags 1 and 2 are made of collagen sponge (for convenience,
3 indicates a sustained-release carrier containing bFGF (indicated by ● for convenience), and 4 indicates a fused portion. The bag for cell transplantation shown in the figure is a PET formed by heat-sealing the ends of two PET meshes.
Collagen sponge 2 and bF in mesh bag 1
It has a shape in which the sustained-release carrier 3 containing GF is uniformly mixed, dispersed, and enclosed.

The artificial pancreas of the present invention is obtained by transplanting pancreatic islets into the above-described bag for cell transplantation of the present invention. The above-mentioned islets may be any of allogeneic islets and allogeneic islets, but it is preferable to transplant allogeneic islets, and it is possible to suppress rejection after implantation / transplantation by transplanting allogeneic islets. it can. The islets may be the islets themselves or the cell mass of the islets. When transplanting xenogeneic islets, rejection can be suppressed by using a conventional immune defense system. The above-mentioned islet transplantation can be performed according to a conventional method. For example, a period (about 1 to 3 weeks) in which the cell transplantation bag of the present invention is embedded in a living body and angiogenesis can be induced inside and outside the bag. ), A method of transplanting pancreatic islets into the bag.

[0016] The artificial pancreas of the present invention may contain nicotinamide. It is known that nicotinamide has an activity of activating pancreatic islets and a function of maintaining functions, and can maintain the function of transplanted islets. The above-mentioned nicotinamide is preferably contained in a sustained-release form, and examples thereof include a form in which the above-mentioned sustained-release carrier containing an angiogenesis-inducing factor is contained and a form in which it is contained in a collagen sponge.

The site for transplanting the cell transplant bag and the artificial pancreas of the present invention is not particularly limited, but is preferably implanted subcutaneously (or intramuscularly). As described above, a major operation is required to transplant a deep part of the body, but if it is subcutaneous or intramuscular, the operation is easy and the burden on the patient can be reduced. In addition, when the transplanted islets lose their function or have a reduced function, it is necessary to refill the islets, but at this time, there is an advantage that the islets can be easily refilled.

Hereinafter, the present invention will be described in more detail with reference to Examples.
However, the present invention is not limited to these examples.
Not. Example 1Production of bag and production of collagen sponge  Polyethylene terephthalate (PET) mesh
A back (2.5 × 2 cm) was prepared. That is, the PET message
Once (provided by Teijin Limited) with acetone once
After washing twice with water for 1 hour each and drying, length 5c
m, 4 cm wide. Folded it
After that, the end is fused with a hot sealer to make a bag
Then, EOG sterilization was performed. In addition, collagen sponge
It was prepared by the following method. 0.1M hydrochloric acid aqueous solution
Into distilled water (500 ml) adjusted to pH 3 by
5 g of freeze-dried collagen (provided by Nippon Ham Co., Ltd.)
And extract from pig skin, enzyme-solubilized extract) and shake
did. While adjusting the pH of this aqueous solution,
Dissolve by standing for 1 week, 1 wt%
An aqueous gen solution was obtained. 50 ml of the obtained collagen aqueous solution
Under ice-cooling, about 7,000 rp with a screw homogenizer
m, stirred for 15 minutes and whipped. Pour this into a container
And immediately put it in a freezer at -80 ° C to freeze the aqueous solution.
And lyophilized overnight. Lyophilized collagens produced
Reduce the pressure of the ponge (10mmHg) for 24 hours at 140 ℃
For thermal crosslinking. Then, EOG sterilization was performed.

Embodiment 2Preparation of gelatin microsphere containing bFGF  Add 375 ml of olive oil to a 1000 ml round bottom flask,
Fixed stirring motor (Shinto Kagaku Co., Ltd.
Teflon (registered trademark) stirring propeller
And fixed together with the flask. Olive oil at 30 ℃
Alkaline treatment with isoelectric point of 4.9 while stirring at 420 rpm
10 ml of a ratine aqueous solution (concentration: about 10%) is dropped, and W / O
A mold emulsion was prepared. After stirring for 10 minutes,
Was cooled to 10-20 <0> C and stirred for 30 minutes. After cooling,
100 ml of acetone and stirred for 1 hour, then centrifuge
The gelatin microspheres were collected by the method. Collected
Wash the microspheres with acetone and
Washing with LOPANOL (hereinafter abbreviated as IPA)
As a result, uncrosslinked gelatin microspheres were obtained. this
Microspheres were dried and stored at 4 ° C. Dry
500% uncrosslinked gelatin microspheres with 0.1% Twee
100ml of glutaraldehyde (0.05%) aqueous solution containing n80
By stirring gently at 4 ° C for 15 hours.
A gelatin crosslinking reaction was performed. After the reaction is completed,
Microspheres are collected by centrifugation and
Washed at 37 ° C for 1 hour with 100 mM glycine aqueous solution containing en80
To stop the crosslinking reaction. After stopping the reaction, crosslink
Gelatin microspheres in order of 0.1% Tween80 aqueous solution,
Washed with IPA, 0.1% Tween80 aqueous solution and twice with distilled water
After lyophilization, dry-crosslink gelatin gel
Cross spheres (average particle diameter 40 μm, water content 95%) were obtained.
50 mg was added to 2 mg of the obtained crosslinked gelatin gel microspheres.
1/15 M phosphate buffer (pH 6) containing μg of bFGF
Is dropped and left at 25 ° C. for 1 hour to obtain bF
GF aqueous solution is permeated into the microspheres and bFGF
An impregnated gelatin microsphere was prepared.

Embodiment 3Angiogenesis test  The following bag was used for diabetes model Lewis male diabetes
Angiogenesis in and around bags implanted subcutaneously in the back of rats
The effect was evaluated. PET mesh bag only (comparative example) Gelatin microsof
PET mesh bag in which air (2 mg) is dispersed and enclosed
(Comparative Example) PET mesh bag enclosing collagen sponge
(Comparative Example) 50 μg of bFGF around collagen sponge and its periphery
Disperse gelatin microspheres (2mg) impregnated with
Enclosed PET mesh bag (cell transplant bag of the present invention)
The diabetic model rat is streptozotocin (55).
mg / kg rat) for 14 days.
Therefore, it was produced. When the blood sugar level was measured,
It was 500 mg / dl.

One and two weeks after the implantation of the bags, the bags were collected and examined visually and histologically. Figure 2 shows the result.
4 to FIG. In the figure, “bag” is PET
Mesh bag, “bFGF” means gelatin microspheres impregnated with bFGF (the same applies hereinafter). FIG.
As shown in FIG. 4, in the cell transplant bag of the present invention, remarkable subcutaneous vascular induction was confirmed at one week. In addition, in the observation for two weeks, the subcutaneous blood vessel induction was further remarkable. Observation under a stereomicroscope demonstrated its subcutaneous vascular guidance more specifically. Further, the presence of new blood vessels was also confirmed by histopathological staining. In contrast, in the comparative example, the presence of new blood vessels was slight. From the above results, strong angiogenesis inside and outside the bag was observed only in the experimental group (bag for transplantation of the present invention) in which the collagen sponge and the gelatin microsphere impregnated with bFGF were sealed in the PET mesh bag.

Embodiment 4Testing for hemoglobin content after implantation  The cell transplant bag of the present invention is used for cell transplantation,
Provides the vascular bed needed to supply oxygen and nutrients to the implanted cells
Inside the bag to show that it is effective to serve
And new tissues in the surrounding tissues,
You must prove that nutrition is provided. So
To prove this, inside and around the embedded bag
The amount of hemoglobin in the tissue was measured. That is, the same as Example 3.
Implant the bag in the same way
And the amount of moglobin in the tissue surrounding the bag was measured. Hemog
Robin is a hemoglobin test Wako (Wako Pure Chemical Industries, Ltd.)
Company). The results are shown in FIGS.
As is clear from the results of FIGS. 5 and 6, hemoglobin
The total amount of collagen sponge in a PET mesh bag
Di and gelatin microspheres impregnated with bFGF
In the enclosed experimental example (cell transplant bag of the present invention)
The highest value was shown.

Embodiment 5Testing blood flow after implantation  50μg of bFGF around collagen sponge and its surroundings
Disperse and seal impregnated gelatin microspheres (2 mg)
PET mesh bag (cell transplant bag of the present invention)
G) fix the laser Doppler sensor inside and implement
Implanted subcutaneously on the back of a diabetic model rat as in Example 3.
Was. Changes in blood flow in the bag at 1, 2 and 3 weeks after implantation
Flow meter (Laser blood flow meter TBF-LNI Uni Co., Ltd.
) Was measured over time. as a result
Is shown in FIG. As shown in FIG. 7, blood flow in the bag
Was found to increase significantly over time.

Embodiment 6Preparation of artificial pancreas and blood glucose measurement test  50μg of bFGF around collagen sponge and its surroundings
Disperse and seal impregnated gelatin microspheres (2 mg)
PET mesh bag (cell transplant bag of the present invention)
G) subcutaneously on the back of a male Lewis diabetic model rat
Implanted. Two weeks later, it was separated from SD male rats.
Transplant pancreatic islets (2,500 / bag) into a bag
The artificial pancreas of the invention was prepared. On the other hand, as a comparative example, bF
PE containing only GF-impregnated gelatin microspheres
Put the T mesh bag in the same manner as above
The pancreatic islets were similarly transplanted two weeks later. above
Changes in blood glucose of treated rats were measured over time.
Was. FIG. 8 shows the result. As shown in FIG.
More than 40 days in rats with artificial pancreas
Blood glucose levels were normalized. On the other hand, bFGF impregnated
This effect is not obtained with microspheres alone (comparative example).
I couldn't. Combining the results of the above examples,
Ming artificial pancreas, collagen and bFGF impregnated gelatin
The presence of both microspheres efficiently angiogenesis
Induces oxygen and nutrients to be supplied to the islets, resulting in
It is considered that the function of the islets was maintained for a long time.

[0025]

The bag for cell transplantation of the present invention contains a sustained-release carrier containing collagen and an angiogenesis-inducing factor, and the angiogenesis inside and outside the bag is promoted by the synergistic action of the two to implant the cell. Since oxygen and nutrients can be supplied to the cells, the function of the transplanted cells can be maintained for a long period of time. Further, the artificial pancreas of the present invention is obtained by transplanting islets into the above-described cell transplant bag, and the function of the transplanted islets is maintained over a long period of time by the above-described effects. And can be used effectively for the treatment of type I diabetes. In particular,
Since the cell transplant bag and the artificial pancreas of the present invention can induce angiogenesis, they can be transplanted subcutaneously or intramuscularly, and the operation is simple and the cells can be easily refilled, which imposes a burden on the patient. Can be reduced.

[Brief description of the drawings]

FIG. 1 is a conceptual diagram of a cut end face at a central portion showing an example of a cell transplant bag of the present invention.

FIG. 2 is a photograph of a tissue section around the bag one week after various PET mesh bags in Example 3 were subcutaneously implanted in the back of a diabetic model rat.

FIG. 3 is a photograph showing macroscopic observation two weeks after various PET mesh bags in Example 3 were subcutaneously implanted in the back of a diabetic model rat.

FIG. 4 is a photograph of a tissue section around the bag two weeks after various PET mesh bags in Example 3 were subcutaneously implanted in the back of a diabetic model rat.

FIG. 5 is a graph showing the hemoglobin content of tissues in a bag one week after various PET mesh bags in Example 4 were implanted subcutaneously on the back of a diabetic model rat.

FIG. 6 is a graph showing hemoglobin levels in tissues surrounding a bag one week after various PET mesh bags were implanted subcutaneously on the back of a diabetic model rat in Example 4.

FIG. 7 is a graph showing blood flow in the bag for cell transplantation of the present invention in Example 5 one, two, and three weeks after subcutaneous implantation of the bag for cell transplantation in the back of a diabetic model rat.

FIG. 8 is a graph showing changes in blood glucose levels in a diabetic model rat to which the artificial pancreas of the present invention and the artificial pancreas of Comparative Example were transplanted in Example 6.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 PET mesh bag 2 Collagen sponge 3 Gelatin microsphere impregnated with bFGF 4 Fusion part

Claims (6)

[Claims] 1. A cell transplant bag comprising a permeable bag made of a polymer material and containing a sustained-release carrier containing collagen and an angiogenesis-inducing factor. 2. The cell transplantation bag according to claim 1, wherein the angiogenesis-inducing factor is basic fibroblast growth factor (bFGF). 3. The bag for cell transplantation according to claim 1, wherein the sustained-release carrier is gelatin microsphere. 4. The cell transplant bag according to claim 1, wherein the collagen is a collagen sponge. 5. The cell transplant bag according to claim 1, which is for subcutaneous implantation. 6. An artificial pancreas wherein a pancreatic islet is transplanted into the cell transplant bag according to any one of claims 1 to 5.