The role of decellularized matrix in directing differentiation of pancreatic progenitor cells in pancreatic endocrine cell fate.

Abstract

The direct differentiation of induced pluripotent stem cells derived from somatic cells and pancreatic progenitor cells could generate functional β-cells that secrete insulin, and are also glucose responsive. However, the cellular signals and interactions between the pancreatic epithelium and its surrounding mesenchyme that govern pancreatic specification and differentiation of endoderm into pancreatic progenitor cells and eventually mature beta cells are not fully understood. In this study, I examined various conditions that would direct the induced pluripotent stem cells (iPSCs) derived from a pdx1: GFP mouse, or normal pancreatic progenitor cells, to predominately β cell fate. It involves the “guided” differentiation of iPSCs to a pancreatic lineage and also the use of a decellularized matrix to induce differentiation into. A decellularized matrix may help mature β-cells since decellularization has been shown to remove all the organ’s cells while preserving the composition and biological activity of the extracellular matrix1. Thus, decelluarization has several advantages: it removes cells to avoid any immune response post-implantation and maintains the native environment and membrane components that provide cellular growth and maturation of β-cells. The results showed that the guided differentiation of iPSCs by activin A induced definitive endodermal and pancreatic progenitor cells. Moreover, the decellularized matrix increased exocrine and endocrine gene expression as compared to gelatin and fibronectin, and assisted survival and maturation of all pancreatic cell types. Hence, this novel approach would be useful to produce insulin-expressing β-cells that are also glucose responsive and generate surrogate cells for diabetes therapy.