Effect of the extracellular matrix on pancreatic endocrine cell function and its biocompatibility in dogs

The effect of the synthetic extracellular matrix (ECM) in a diffusion chamb er for a bioartificial endocrine pancreas (Bio-AEP) on pancreatic endocrine cells in vitro and its biocompatibility in dogs were investigated. Two dif ferent types of ECM were used: type I collagen treated with low antigen (ty pe I LA), and reconstituted basement membrane matrix (Matrigel) derived fro m Englbreth-Holm-Swarm (EHS) mouse sarcoma. Matrigel contains growth and di fferentiation 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 x 10(7) 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 an d PE cells was implanted into the abdominal cavity of a pancreatectomized d iabetic dog, the exogenous insulin requirement for maintaining normoglycemi a was reduced for the first 4 weeks. However, after 6 weeks of implantation , fasting blood glucose levels suddenly increased. Laparotomy revealed enca psulated Bio-AEP with thick fibrous tissue. Following removal of the Bio-AE P from the abdominal cavity, another Bio-AEP containing type I LA and PE ce lls was implanted into the same dog. The exogenous insulin requirement was gradually decreased to almost half that of preimplantation levels. Bio-AEPs containing type I LA or Matrigel, but not PE cells, were implanted into th e abdominal cavities of four healthy dogs. After 4 weeks of implantation, t he Bio-AEP with Matrigel was encapsulated with fibrous tissue similar to th at in the diabetic dog, but the Bio-AEP with type I LA was not. These resul ts indicate that Matrigel may be incompatible with dogs and that the type I LA is more suitable for Bio-AEP.