1. Human Glial Progenitor Cells Effectively Remyelinate the Demyelinated Adult Brain.
- Author
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Windrem MS, Schanz SJ, Zou L, Chandler-Militello D, Kuypers NJ, Nedergaard M, Lu Y, Mariani JN, and Goldman SA
- Subjects
- Animals, Cell Differentiation, Humans, Mice, Brain physiopathology, Demyelinating Diseases genetics, Neuroglia metabolism, Stem Cells metabolism
- Abstract
Neonatally transplanted human glial progenitor cells (hGPCs) can myelinate the brains of myelin-deficient shiverer mice, rescuing their phenotype and survival. Yet, it has been unclear whether implanted hGPCs are similarly able to remyelinate the diffusely demyelinated adult CNS. We, therefore, ask if hGPCs could remyelinate both congenitally hypomyelinated adult shiverers and normal adult mice after cuprizone demyelination. In adult shiverers, hGPCs broadly disperse and differentiate as myelinating oligodendrocytes after subcortical injection, improving both host callosal conduction and ambulation. Implanted hGPCs similarly remyelinate denuded axons after cuprizone demyelination, whether delivered before or after demyelination. RNA sequencing (RNA-seq) of hGPCs back from cuprizone-demyelinated brains reveals their transcriptional activation of oligodendrocyte differentiation programs, while distinguishing them from hGPCs not previously exposed to demyelination. These data indicate the ability of transplanted hGPCs to disperse throughout the adult CNS, to broadly myelinate regions of dysmyelination, and also to be recruited as myelinogenic oligodendrocytes later in life, upon demyelination-associated demand., Competing Interests: Declaration of Interests S.A.G. is a co-founder of the Oscine Corporation and receives sponsored research support and consulting income from Oscine. S.A.G. and M.W. are co-inventors on patents covering the therapeutic uses of human glial progenitors, which have been licensed by the University of Rochester to Oscine. None of the other authors have any known conflicts of interest in regard to this work., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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