Extracellular Matrix Mediated Differentiation of Human Embryonic Stem Cells: Differentiation to Insulin Secreting Beta Cells
Stem cells have tremendous potential for treating various human diseases. Protocols have been established to differentiate stem cells into specific lineages through the provision of signals in the form of growth factors, cytokines, or small molecules. Herein we investigate an alternative strategy for directed differentiation of human embryonic stem cells (hESCs) extracellular matrix (ECM) mediated differentiation. Decellularized ECM and conditioned media from the appropriate committed cell lines are used to differentiate stem cells to the required phenotype. Applying this strategy to differentiate hESCs to pancreatic beta cells, we have obtained functional cells that secreted insulin in a glucose responsive manner, and were able to recover normoglycemia in a streptozotocin (STZ) induced diabetic mouse model. ECM mediated differentiation was also demonstrated to be effective for the differentiation of hESCs into kidney tubule cells and cardiomyocytes. Gene expression studies suggested the involvement of in.