Improving the Differentiation of human pluripotent stem cells to beta-cells.

Abstract

Human pluripotent stem cells (hPSCs) have the ability to differentiate into any cell type within the body, thus holding the potential for treating the beta-cell loss in type 1 diabetes through a cell replacement therapy. Though effective protocols have been produced for creating beta-cells from hPSCs, the efficiency of this process can be improved to yield more beta-cells. Here, we hypothesized that the addition of the hormones prolactin and human growth hormone to our established differentiation protocol will result in more beta-cells or beta-cell progenitors. This is based on work with isolated pancreatic islets, which showed that these hormones are able to stimulate proliferation of mature beta-cells and increase islet volume. And as much of the work with these hormones has been in rodent islets, we also present data showing that prolactin is able to stimulate cell division and islet growth in human islets. Any influences of the hormones were observed through gene expression analysis and a cell-death assay. This work will inform future work on creating beta-cells from hPSCs, and hopefully move the potential therapy closer to the clinic.