Inside the Matrix: A pancreas-derived hydrogel for the culture of hiPSC-derived pancreatic endocrine cells

Abstract

Abstract Stem cell-derived β-cells (SC-BCs) display a potential source for curing diabetes. Up to now, in vitro generated SC-BCs display an immature phenotype and lack important features in comparison to their bona-fide counterparts. Transplantation into a living animal promotes SC-BCs maturation, indicating that components of the in vivo microenvironment trigger final SC-BCs development. Here, we investigated whether cues of the pancreas specific extracellular matrix (ECM) can improve the differentiation of human induced pluripotent stem cells (hiPSCs) towards β-cells in vitro. To this aim, a pancreas specific ECM (PanMa) hydrogel was generated from decellularized pancreas of the pig and its effect on the differentiation and maturation of hiPSC-derived pancreatic hormone expressing cells (HECs) tested. The produced hydrogel solidified upon neutralization at 37°C with gelation kinetics similar to Matrigel. Cytocompatibility of the PanMa hydrogel was demonstrated for a culture duration of 21 days. Encapsulation and culture of HECs in the PanMa hydrogel over 7 days resulted in a stable gene and protein expression of β-cell markers, but did not improve β-cell maturation. In conclusion, the study describes the production of a PanMa hydrogel, which provides the basis for the development of ECM hydrogels that are more adapted to the demands of SC-BCs.