INTRODUCTION: Many cytoprotective agents have been reported to improve islet isolation and transplantation outcomes. However, several of these agents improve all cell subsets within an islet preparation; selection of non-beta-cell components (eg, acinar cells) may have a negative effect on beta-cell function and survival. In this study, we examined the effect of prolactin (PRL) supplementation in the culture medium to determine whether it exerted beta-cell-selective cytoprotection on islet viability and function. MATERIALS AND METHODS: Human islets were precultured with or without recombinant human PRL (500 microg/L) for 48 hours. The fractional viability and cellular composition of non-beta-cell and beta-cell-specific components were assessed using FACS and Laser Scanning Cytometry (LSC). Islet potency was assessed in vivo by transplantation into chemically induced diabetic immunodeficient mice. RESULTS: The relative viable beta-cell mass and the relative islet beta-cell content in the PRL group were 28% higher (P = .018) and 19% higher (P = .029) than the control group, respectively. All transplanted mice achieved normoglycemia in both groups, indicating that PRL treatment did not alter islet function. CONCLUSION: PRL treatment improved beta-cell-specific viability and survival of human islets in vitro. The development of novel beta-cell-specific cytoprotective strategies may be of assistance in improving islet transplantation.
INTRODUCTION: Many cytoprotective agents have been reported to improve islet isolation and transplantation outcomes. However, several of these agents improve all cell subsets within an islet preparation; selection of non-beta-cell components (eg, acinar cells) may have a negative effect on beta-cell function and survival. In this study, we examined the effect of prolactin (PRL) supplementation in the culture medium to determine whether it exerted beta-cell-selective cytoprotection on islet viability and function. MATERIALS AND METHODS:Human islets were precultured with or without recombinant humanPRL (500 microg/L) for 48 hours. The fractional viability and cellular composition of non-beta-cell and beta-cell-specific components were assessed using FACS and Laser Scanning Cytometry (LSC). Islet potency was assessed in vivo by transplantation into chemically induced diabetic immunodeficientmice. RESULTS: The relative viable beta-cell mass and the relative islet beta-cell content in the PRL group were 28% higher (P = .018) and 19% higher (P = .029) than the control group, respectively. All transplanted mice achieved normoglycemia in both groups, indicating that PRL treatment did not alter islet function. CONCLUSION:PRL treatment improved beta-cell-specific viability and survival of human islets in vitro. The development of novel beta-cell-specific cytoprotective strategies may be of assistance in improving islet transplantation.
Authors: Lisa Balbach; Henri Wallaschofski; Henry Völzke; Matthias Nauck; Marcus Dörr; Robin Haring Journal: BMC Endocr Disord Date: 2013-03-21 Impact factor: 2.763