An improved method for generating oligodendrocyte progenitor cells from murine induced pluripotent stem cells

Abstract

Cell based therapies aiming to restore myelin in the central nervous system offer great hope for treatment of numerous conditions, ranging from multiple sclerosis and the leukodystrophies, to traumatic CNS injury. The oligodendrocyte progenitor cell (OPC) gives rise to functional oligodendrocytes following transplantation into dysmyelinated regions of the central nervous system, and as such represents a candidate for potential therapeutic applications. It can be generated by directed differentiation of a variety of pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells. The iPS cell is an ideal source for derivation of OPCs, as it offers the advantage of autologous transplants, and a model to study the biology and pathology of OPCs and oligodendrocytes. Existing protocols for deriving OPCs from mouse iPS cells, although a valuable model, are inefficient and not easily reproducible. We improved upon the existing differentiation protocols to increase their consistency and yield of OPCs, by modifying and combining several published methods. We demonstrate robustness of our new method by generating OPCs from several different pluripotent stem cell lines and demonstrating that the OPCs further develop to form functional oligodendrocytes in vivo.