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

Nature Biotechnology volume 29, pages 934–941 (2011)Cite this article

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Abstract

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.

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Figure 1: CD140a/PDGFRα identifies a proliferating OPC in fetal cortex and intermediate zone.
Figure 2: CD140a/PDGFRα recognizes a population of cells in the fetal brain that accumulates with gestational age in the intermediate zone and cortex.
Figure 3: CD140a/A2B5/PSA-NCAM cytometry.
Figure 4: CD140a+ cells mature primarily as oligodendrocytes but can be maintained as bipotential progenitors.
Figure 5: CD140a+ cells efficiently myelinate shiverer axons.
Figure 6: CD140a+ OPCs myelinate more effectively compared with A2B5+ OPCs.

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Acknowledgements

This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) grants R01NS039559, R01NS75345 and P01NS050315, the National Multiple Sclerosis Society, the New York State Stem Cell Research Board (NYSTEM), the Adelson Medical Research Foundation, and the Mathers Charitable Foundation. We would like to thank X.-J. Li for technical support, and M. Zanche, A. Cardillo and the University of Rochester Medical Center Functional Genomics core for Affymetrix and Taqman array support. O4 supernatant was a gift of R. Bansal and the late S. Pfeiffer (University of Connecticut).

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Authors and Affiliations

  1. Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA

    Fraser J Sim, Crystal R McClain, Steven J Schanz, Tricia L Protack, Martha S Windrem & Steven A Goldman

  2. Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA

    Fraser J Sim & Steven A Goldman

  3. Department of Pharmacology, State University of New York at Buffalo, Buffalo, New York, USA

    Fraser J Sim

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Contributions

F.J.S. directed both the in vitro experiments and genomics analysis; C.M. planned and performed the in vitro studies with F.J.S., and conducted the assessment of OPC ontogeny; S.S. performed the transplants of A2B5+ and CD140+ cells into shiverer mice; T.L.P. assisted F.J.S. and C.M. in the in vitro studies and FACS analysis; M.S.W. directed the comparative assessment of myelination by A2B5 and CD140a cells in vivo; S.A.G. co-designed the experiments, co-analyzed the data with F.J.S. and M.S.W. and wrote the paper together with the co-authors.

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Correspondence to Fraser J Sim or Steven A Goldman.

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Competing interests

S.A.G. and F.J.S. have a patent application pending on the use of CD140a-sorted oligodendrocyte progenitor cells in therapeutic remyelination.

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Sim, F., McClain, C., Schanz, S. et al. CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells. Nat Biotechnol 29, 934–941 (2011). https://doi.org/10.1038/nbt.1972

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