Assessment and modeling of poly(vinyl alcohol) bioartificial pancreas in vivo.

Abstract

Pancreatic islets surrounded by a semipermeable membrane to prevent an immune response by the host immunosystem is a potential way of treating type I diabetes mellitus. Our previous in vitro studies have demonstrated that poly(vinyl alcohol) (PVA) membranes satisfy the basic requirements for a bioartificial pancreas. This study was designed to evaluate the performance of PVA tubular membrane chambers containing islets in vivo. When the m-2 type of PVA chamber was implanted into streptozotocin-induced diabetic rats, nonfasting blood glucose levels dropped from 500 +/- 35 mg/dl to the lowest value 210 +/- 22 mg/dl. Furthermore, the performance of the bioartificial pancreas can be enhanced by the increased numbers of implanted chambers. If three m(-2) chambers were implanted, nonfasting blood glucose levels in the diabetic rats decreased to 130-160 mg/dl and such a low blood glucose value was maintained for 1 month. This indicates that implanting three m-2 chambers in the diabetic rats could provide improved permeability of insulin to normalize blood glucose levels and improved survival of islets from the immune system of the recipient. For improving the design of the bioartificial pancreas, a mathematical model was developed to account for the changes in blood glucose levels of the diabetic rats. We demonstrated such a mathematical analysis was helpful to understand the characteristics of islet inside an artificial environment.