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EP-4019025-B1 - COMPOSITION COMPRISING MICROCAPSULE AND CELL STRUCTURE

EP4019025B1EP 4019025 B1EP4019025 B1EP 4019025B1EP-4019025-B1

Inventors

  • NAKAMURA KENTARO
  • KOGAWA Ryo
  • TAKEGAMI RYUTA
  • MOCHIZUKI YUSUKE

Dates

Publication Date
20260506
Application Date
20200821

Claims (14)

  1. A composition comprising at least: (a) a microcapsule containing a polymer hydrogel; (b) a cell structure containing a biocompatible polymer block and a cell, in which a plurality of biocompatible polymer blocks are arranged in gaps between a plurality of cells; and (c) one or more selected from an insulin-secreting cell, a pancreatic islet cell, and a pancreatic islet, wherein at least a part of the cell structures and at least a part of the one or more selected from an insulin-secreting cell, a pancreatic islet cell, or a pancreatic islet are encapsulated in the microcapsules, wherein the cell is a somatic stem cell, and wherein the biocompatible polymer blocks are constituted by a polymer composed of at least one biodegradable material selected from the group consisting of a polypeptide, a polylactic acid, a polyglycolic acid, polylactic acid-co-glycolic acid (PLGA), hyaluronic acid, glycosaminoglycan, proteoglycan, chondroitin, cellulose, agarose, carboxymethyl cellulose, chitin, and chitosan.
  2. The composition according to claim 1, wherein the cell is a mesenchymal stem cell.
  3. The composition according to claims 1 or 2, wherein at least a part of the cell structures are present outside the microcapsules.
  4. The composition according to any one of claims 1 to 3, wherein 50% or more of the cell structures are present inside the microcapsules.
  5. The composition according to any one of claims 1 to 4, wherein 50% or more of the (c) one or more selected from an insulin-secreting cell, a pancreatic islet cell, or a pancreatic islet are encapsulated in the microcapsules.
  6. The composition according to any one of claims 1 to 5, wherein the composition contains a pancreatic islet, and a circle-equivalent diameter size of the cell structure is 0.5 times or more and 4 times or less with respect to the pancreatic islet.
  7. The composition according to any one of claims 1 to 6, wherein the composition contains a pancreatic islet, and a number ratio of the cell structures to the pancreatic islets, which are encapsulated in one microcapsule, is in a range of 0.1:1.0 to 1.0:0.1.
  8. The composition according to any one of claims 1 to 7, wherein a main component of the microcapsule is alginic acid.
  9. The composition according to any one of claims 1 to 8, wherein the microcapsule is coated with poly-L-ornithine.
  10. The composition according to any one of claims 1 to 9, wherein the composition is used for transplantation into a living body.
  11. The composition according to any one of claims 1 to 10, wherein the composition is for intraperitoneal transplantation or subcutaneous transplantation.
  12. The composition according to claim 11, wherein the composition is for subcutaneous transplantation.
  13. The composition according to any one of claims 1 to 12, wherein the composition is a pharmaceutical composition.
  14. The composition according to any one of claims 1 to 13, wherein the composition is a pharmaceutical composition for treatment of diabetes.

Description

Technical Field The present invention relates to a composition containing at least microcapsules, cell structures and one or more selected from an insulin-secreting cell, a pancreatic islet cell, and a pancreatic islet, in which at least a part of the cell structures and at least a part of the one or more selected from an insulin-secreting cell, a pancreatic islet cell, or a pancreatic islet are encapsulated in the microcapsules. Related Art There is a method called pancreatic islet transplantation as an advanced treatment method that can be a radical treatment for diabetes. The pancreatic islet transplantation is an advanced treatment method that eliminates the need for insulin injection in diabetes for each meal, and specifically, it is a treatment method of transplanting pancreatic islets (insulin-secreting tissue) isolated from the pancreas of the organ donor. However, it is said that the pancreatic islet transplantation is difficult to become general medical treatment due to the practical problem of a shortage of organ donors. As a means to solve this problem, attempts to transplant pancreatic islets derived from heterologous animals (mostly derived from pigs), or attempts to produce pancreatic islet cells from embryonic stem cells (ES cells) or induced pluripotent stem cells (iPS cells) have been studied. Heterogeneous pancreatic islets are considered to be a source of pancreatic islets closest to industrialization. Patent Document 1 discloses a method of treating diabetes by using neopancreatic islets containing (a) dedifferentiated pancreatic islet cell and mesenchymal stem cell and/or an adipose stem cell, or (b) redifferentiated mesenchymal stem cell which is treated to promote redifferentiation of a cell and/or an adipose stem cell. In addition, immunoisolation of a cell with an alginate capsule is described in Non-Patent Document 1. Non-Patent Document 2 describes alginate microencapsulated islets and the provision of a permeation barrier between the graft tissue and the host immune system. Prior Art Documents Patent Documents Patent Document 1: JP2018-530603A Non-Patent Documents Non-Patent Document 1: Stephan, S et al. (2005) Diabetes. 54 (3): 687-693Non-Patent Document 2: Darrabie, M. D. et al. (2005) Biomaterials 26 :6846-6852 SUMMARY OF THE INVENTION There are two problems in applying heterologous pancreatic islets to treatment. The first problem is the "avoidance of immune rejection". This is a problem in that the administered heterologous pancreatic islets are eliminated by the recipient's immune system. The use of immunosuppressive agents can be considered as a solution to the above problem; however, it cannot be said to be a practical solution since it involves an economic burden due to the permanent use of expensive immunosuppressive agents and a physical burden due to side effects. Regarding the avoidance of immune rejection, attempts to immunoisolate a cell with an alginate capsule have been studied, for example, as in Stephan, S et al. (2005) Diabetes. 54 (3): 687-693. However, as a practical problem, it is recognized as a problem that pancreatic islets cannot continue to exhibit their sustainable functions only by immunoisolation with a capsule or the like. The second problem is the "avoidance of poor engraftment of pancreatic islets". From the viewpoint of convenience, simple subcutaneous administration is urgently desired in actual medical treatment; however, it has been known that the engraftment rate of pancreatic islets is remarkably low in the subcutaneous tissue, and thus it has been difficult to realize subcutaneous transplantation. In addition, this problem of poor engraftment of pancreatic islets becomes more apparent in pancreatic islets immunoisolated with such a capsule described above. A capsule or the like, which is used in the immunoisolation technique, has a function similar to a semipermeable membrane, which allows insulin to permeate while blocking the host's immune response to the pancreatic islets; however, in reality, such performance similar to a semipermeable membrane causes permeation inhibition of nutrients, and it has been well known that pancreatic islets inside the capsule undergo necrosis or undergo cell death through apoptosis. An object to be achieved by the present invention is to provide a composition containing at least microcapsules and cell structures, where the composition can exhibit a high treatment effect in a case of being transplanted into a living body. As a result of diligent studies to achieve the above object, the inventors of the present invention have found that in a case where a composition contains microcapsules containing a polymer hydrogel and contains cell structures containing a biocompatible polymer block and a mesenchymal stem cell, and in the composition, in a case where the cell structures are encapsulated in the microcapsules, heterologous cells can be engrafted and a treatment effect can be exhibited. The present inventio