Oligodendrogenesis from neural stem cells: perspectives for remyelinating strategies

Abstract

Mobilization of remyelinating cells spontaneously occurs in the adult brain. These cellular resources are specially active after demyelinating episodes in early phases of multiple sclerosis (MS). Indeed, oligodendrocyte precursor cells (OPCs) actively proliferate, migrate to and repopulate the lesioned areas. Ultimately, efficient remyelination is accomplished when new oligodendrocytes reinvest nude neuronal axons, restoring the normal properties of impulse conduction. As the disease progresses this fundamental process fails. Multiple causes seem to contribute to such transient decline, including the failure of OPCs to differentiate and enwrap the vulnerable neuronal axons. Regenerative medicine for MS has been mainly centered on the recruitment of endogenous self-repair mechanisms, or on transplantation approaches. The latter commonly involves grafting of neural precursor cells (NPCs) or neural stem cells (NSCs), with myelinogenic potential, in the injured areas. Both strategies require further understanding of the biology of oligodendrocyte differentiation and remyelination. Indeed, the success of transplantation largely depends on the pre-commitment of transplanted NPCs or NSCs into oligodendroglial cell type, while the endogenous differentiation of OPCs needs to be boosted in chronic stages of the disease. Thus, much effort has been focused on finding molecular targets that drive oligodendrocytes commitment and development. The present review explores several aspects of remyelination that must be considered in the design of a cell-based therapy for MS, and explores more deeply the challenge of fostering oligodendrogenesis. In this regard, we discuss herein a tool developed in our research group useful to search novel oligodendrogenic factors and to study oligodendrocyte differentiation in a time- and cost-saving manner.

Keywords: 2′,3′-cyclic nucleotide-3′-phosphodiesterase; CNP; CNS; CNS repair; CPZ; DG; DIV; EAE; MAG; MBP; MS; MSCs; NGF; NPCs; NSCs; OPCs; PDGFRα; PLP; PNS; SVZ; T3; T3 receptors; TRs; cell therapy; central nervous system; cuprizone; days in vitro; dentate gyrus; eGFP; eNSCs; embryonic neural stem cells; enhanced-green fluorescent protein; experimental autoimmune encephalomyelitis; iPSCs; inducible pluripotent stem cells; mesenchymal stem cells; multiple sclerosis; myelin basic protein; myelin-associated glycoprotein; nerve growth factor; neural precursor cells; neural stem cells; oligodendrocyte precursor cells; oligodendrocytes; peripheral nervous system; platelet-derived growth factor receptor alpha; proteolipid protein; remyelination; subventricular zone; triiodothyronine.