Experimental Hybrid Islet Transplantation: Application of Polyvinyl Alcohol Membrane for Entrapment of Islets

In this study, we first examined in vitro a polyvinyl alcohol membrane to be used to contain hybrid islet cells, and second we tested a bioartificial pancreas with entrapment of pancreatic islets in polyvinyl alcohol membrane in rats with experimentally induced diabetes. The permeability of the polyvinyl alcohol membrane to different substances was studied in a two-cell chamber system. Glucose, insulin, and nutrients passed through the membrane easily, whereas the passage of immunoglobulin G was completely prevented, indicating that this membrane could be effective in protecting the bioartificial pancreas from immunorejection. Approximately 2,000 islets collected from three Sprague-Dawley rats were enclosed in a mesh-reinforced polyvinyl alcohol tube and transplanted into the peritoneal cavity of six Wistar rats with streptozotocin-induced diabetes. Their nonfasting serum glucose levels were significantly decreased for at least 12 days. Six diabetic rats receiving intra-peritoneal transplantation of free islets without the tube showed a slight but significant decrease in nonfasting serum glucose levels for only 3 days. One diabetic rat with transplantation of the bioartificial pancreas had a significant and sustained decrease in nonfasting glucose levels from pretransplanted levels of 440–500 mg/dl to a mean value of 162 ± 13 mg/dl for over 3 months without immunosuppression. The bioartificial pancreas was then removed, and glucose levels gradually increased to over 500 mg/dl. The results of the present study suggest that a bioartificial pancreas with entrapment of islets in a polyvinyl alcohol membrane could be a promising therapeutic approach to diabetes mellitus.

[1]  B A Solomon,et al.  Biohybrid artificial pancreas: long-term implantation studies in diabetic, pancreatectomized dogs. , 1991, Science.

[2]  B. Ahrén,et al.  Insulin secretion in streptozotocin-diabetic rats transplanted with immunoisolated islets. , 1991, Transplantation.

[3]  B A Solomon,et al.  Successful treatment of diabetes with the biohybrid artificial pancreas in dogs. , 1991, Transplantation.

[4]  P. Lacy,et al.  Results of our first nine intraportal islet allografts in type 1, insulin-dependent diabetic patients. , 1991, Transplantation.

[5]  A. Sun,et al.  Reversal of Diabetes in BB Rats by Transplantation of Encapsulated Pancreatic Islets , 1990, Diabetes.

[6]  A. Sun,et al.  In vitro culture and transplantation of encapsulated human fetal islets as an artificial endocrine pancreas. , 1989, ASAIO transactions.

[7]  M. Field,et al.  Pancreatic islet isolation in rats with ductal collagenase distention, stationary digestion, and dextran separation. , 1988, Transplantation.

[8]  Y. Ikada,et al.  Cell Attachment to Various Polymer Surfaces , 1986 .

[9]  S. Krane,et al.  Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin 1). , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[10]  F. Lim,et al.  Microencapsulated islets as bioartificial endocrine pancreas. , 1980, Science.

[11]  A. Sun,et al.  The Use, in Diabetic Rats and Monkeys, of Artificial Capillary Units Containing Cultured Islets of Langerhans (Artificial Endocrine Pancreas) , 1977, Diabetes.

[12]  M J Lysaght,et al.  Artificial pancreas using living beta cells:. effects on glucose homeostasis in diabetic rats. , 1977, Science.

[13]  G. Hastings.  Polymers in medicine. , 1971, Chemistry in Britain.