Generation of Human Oligodendrocyte Progenitors for Treatment of Demyelinating Diseases and Spinal Cord Injury

Abstract

Glial cells play a critical role in the development and function of the mammalian central nervous system (CNS). Among other roles, these cells provide the myelin sheath needed for the efficient propagation of impulses along nerve fibers, provide trophic support for neuronal cells, and remove toxins and excess neurotransmitters from the interstitial space. Transplantation of glial cells or glial progenitors into the diseased or injured CNS can provide therapeutic benefits. However, generation of therapeutically useful quantities of glia, in particular oligodendrocytes, is technically challenging. Furthermore, generation of glial precursors from sources such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells poses potential safety risks due to the tumorigenic potential of undifferentiated cells. Here we report a method that enables the efficient generation and expansion of glial precursors from tissue-restricted neural stem cells (NSC). NSC-derived glial precursors can be expanded extensively in culture and retain the capacity to differentiate into oligodendrocytes and astrocytes in vitro and in vivo. Upon transplantation into different animal models of demyelination a substantial proportion of these cells become oligodendrocytes with the capacity to myelinate host axons. These results demonstrate that tissue-restricted human neural stem cells can serve as an efficient source for myelinating oligodendrocytes with therapeutic potential.