Optimization of In Vitro Cultures of Neonatal Porcine Islets Pre-transplantation

Abstract

Islet transplantation is an attractive method to achieve blood glucose homeostasis. However, β-cell function declines over time. Therefore, it is necessary to explore strategies to enhance the β-cell mass and function. Also, because there is a severe shortage of human cadaver tissue, alternative sources of insulin secreting tissue need to be examined. Neonatal porcine islet (NPI) tissue has emerged as an attractive alternative source of β-cells. The aim of this thesis was to optimize the culturing conditions of NPIs pre-transplantation so that the available tissue can be used as efficiently and economically as possible. The results from this study indicate that the treatment of NPI cultures with z-VAD-FMK, a pan caspase inhibitor and general protease inhibitor significantly enhances β-cell survival. Additionally, the optimum length of culturing NPIs pre-transplantation appears to be 3-5 days. Since widespread cell death stimulates immunogenic response, this treatment also has the potential benefit of reducing immunosuppression needs in the recipient.