CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells

Abstract

Oligodendrocyte progenitors capable of myelination in myelin-deficient mice have been isolated from human fetal brain cells, but at low purity. Sim et al. show that sorting based on PDGFRα expression yields a purer population of myelinogenic cells free of neuronal and committed astrocyte cells. Experimental animals with myelin disorders can be treated by transplanting oligodendrocyte progenitor cells (OPCs) into the affected brain or spinal cord. OPCs have been isolated by their expression of gangliosides recognized by mAb A2B5, but this marker also identifies lineage-restricted astrocytes and immature neurons. To establish a more efficient means of isolating myelinogenic OPCs, we sorted fetal human forebrain cells for CD140a, an epitope of platelet derived growth factor receptor (PDGFR)α, which is differentially expressed by OPCs. CD140a+ cells were isolated as mitotic bipotential progenitors that initially expressed neither mature neuronal nor astrocytic phenotypic markers, yet could be instructed to either oligodendrocyte or astrocyte fate in vitro. Transplanted CD140a+ cells were highly migratory and robustly myelinated the hypomyelinated shiverer mouse brain more rapidly and efficiently than did A2B5+cells. Microarray analysis of CD140a+ cells revealed overexpression of the oligodendroglial marker CD9, suggesting that CD9+/CD140a+ cells may constitute an even more highly enriched population of myelinogenic progenitor cells.