EndoC-ßH3 pseudoislets are suitable for intraportal transplantation in diabetic mice

Abstract

Background: Islet or β-cell transplantation is a therapeutical approach to substitute the insulin-producing cells which are abolished in type 1 diabetes mellitus. The shortage of human islets as well as the complicated and costly isolation process limit the application of these techniques in daily clinical practice. EndoC-βH is a human β-cell line that readily forms aggregates termed pseudoislets, providing an alternative to primary human islets or β-cells. Methods: EndoC-βH3 cells were seeded and incubated to form pseudoislets. Their insulin secretion was analyzed by ELISA and compared with cell monolayers. Pseudoislets were transplanted into streptozotocin-treated NMRi nu/nu mice. Blood glucose was monitored before and after transplantation and compared with wild types. Grafts were analyzed by immunohistology. Results: This study shows that EndoC-βH cells are able to form pseudoislets by aggregation, leading to an enhanced glucose stimulated insulin secretion in vitro. These pseudoislets were then successfully transplanted into the livers of diabetic mice and produced insulin in vitro. Blood glucose levels of the streptozocin-treated recipient mice were significantly decreased when compared to pre-transplantation and matched the levels found in control mice. Conclusion: We suggest pseudoislets aggregated from EndoC-βH cells as a valuable and promising model for islet transplantation research.