Microvesicles facilitate the differentiation of mesenchymal stem cells into pancreatic beta-like cells via miR-181a-5p/150-5p

Transplantation of pancreatic islet cells is a promising strategy for the long-term treatment of type 1 diabetes (T1D). The stem cell-derived beta cells showed great potential as substitute sources of transplanted pancreatic islet cells. However, the current efficiency of stem cell differentiation still cannot match the requirements for clinical transplantation. Here, we report that microvesicles (MVs) from insulin-producing INS-1 cells could induce mesenchymal stem cell (MSC) differentiation into pancreatic beta-like cells. The combination of MVs with small molecules, nicotinamide and insulin-transferrin-selenium (ITS), dramatically improved the efficiency of MSC differentiation. Notably, the function of MVs in MSC differentiation requires their entry into MSCs through giant pinocytosis. The MVs-treated or MVs combined with small molecules-treated MSCs show pancreatic betalike cell morphology and response to glucose stimulation in insulin secretion. Using high throughput small RNAsequencing, we found that MVs induced MSC differentiation into the beta-like cells through miR-181a-5p/1505p. Together, our findings reveal the role of MVs or the MV-enriched miR-181a-5p/150-5p as a class of biocompatible reagents to differentiate MSCs into functional beta-like cells and demonstrate that the combined usage of MVs or miR-181a-5p/150-5p with small molecules can potentially be used in making pancreatic islet cells for future clinical purposes.