Development of a polysulfone hollow fiber vascular bio-artificial pancreas device for in vitro studies

Abstract

A system for vascular hollow fiber bio-artificial pancreas development, optimization and in vitro testing was implemented and operated in a simple and fully described manner, allowing other researchers to test a variety of experimental conditions (different biomaterials, biologic tissue, addition of proteins or other adjuvants). In this work, a polysulfone hollow fiber was used as bioprotective material. Two different cell sources were co-immobilized with agarose microspheres in and experimented with the membrane device: rat islets of Langerhans and mouse β-TC-3 insulinoma cells. The results obtained with islets of Langerhans were used as islet comparable insulin-release data. Beta-TC-3 cells were mainly used in these studies, due to higher control and reproducibility of cell number and behavior: addition of hemoglobin was beneficial for sustained cell viability, especially during cell insertion in the device (viability assessed by β-TC-3 lactate dehydrogenase activity in the recirculating culture medium); cells did not adhere to the polysulfone membrane (assessed by SEM observation of membrane samples from dynamic cultures). Comparable device functionality and insulin-release results were attained with both cell types: device functionality was maintained for 7–9 days and maximum insulin-release during dynamic glucose challenges were 2.6 × 10 −3 ± 7 × 10 −5 μU/β-cell × 8 h, with islets, and 9.3 × 10 −4 ± 2 × 10 −5 μU/β-cell × 2 h, with β-TC-3 cells.