Effect of the Extracellular Matrix on Pancreatic Endocrine Cell Function and its Biocompatibility in Dogs

Cell Transplantation

Article

Kenichiro Ono¹  Shiho Ishikawa¹  Naoaki Matsuki¹  Hiroyuki Ogawa²  Kazuya Edamura³  Nobuo Sasaki⁴  Hisako Ohgawara⁵  Yukiko Iwami⁵  Koko Nasu⁵  Ayako Sato⁶ 

[1] Laboratories of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo;Laboratories of Veterinary Emergency Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo;Laboratories of Veterinary Emergency Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo;Medical Research Institute, School of Medicine, Tokyo Women's Medical University;Laboratories of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo;Medical Research Institute, School of Medicine, Tokyo Women's Medical University;Medical Research Institute, School of Medicine, Tokyo Women's Medical University;Institute of Applied Biochemistry, University of Tsukuba;

关键词: Bioartificial endocrine pancreas;    Biocompatibility;    Diffusion chamber;    Extracellular matrix;   

DOI  :  10.3727/000000001783986639

来源: Sage Journals

【 摘 要 】

The effect of the synthetic extracellular matrix (ECM) in a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP) on pancreatic endocrine cells in vitro and its biocompatibility in dogs were investigated. Two different types of ECM were used: type I collagen treated with low antigen (type I LA), and reconstituted basement membrane matrix (Matrigel) derived from Englbreth-Holm-Swarm (EHS) mouse sarcoma. Matrigel contains growth and differentiation factors and cell adhesion molecules such as laminin, heparan sulfate proteoglycan, and entactin. Purified porcine pancreatic endocrine (PE) cells were suspended in type I LA or Matrigel and then placed into a 12-well culture plate (4 × 107 cells/ml · gel/well). The insulin accumulation from PE cells in Matrigel was significantly greater than that in type I LA (9.3 ± 3.6 mU/well vs. 2.3 ± 1.3 mU/well). When Bio-AEP with Matrigel and PE cells was implanted into the abdominal cavity of a pancreatectomized diabetic dog, the exogenous insulin requirement for maintaining normoglycemia was reduced for the first 4 weeks. However, after 6 weeks of implantation, fasting blood glucose levels suddenly increased. Laparotomy revealed encapsulated Bio-AEP with thick fibrous tissue. Following removal of the Bio-AEP from the abdominal cavity, another Bio-AEP containing type I LA and PE cells was implanted into the same dog. The exogenous insulin requirement was gradually decreased to almost half that of preim-plantation levels. Bio-AEPs containing type I LA or Matrigel, but not PE cells, were implanted into the abdominal cavities of four healthy dogs. After 4 weeks of implantation, the Bio-AEP with Matrigel was encapsulated with fibrous tissue similar to that in the diabetic dog, but the Bio-AEP with type I LA was not. These results indicate that Matrigel may be incompatible with dogs and that the type I LA is more suitable for Bio-AEP.

【 授权许可】

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