Neonatal Chimerization with Human Glial Progenitor Cells Can Both Remyelinate and Rescue the Otherwise Lethally Hypomyelinated Shiverer Mouse

Martha S. Windrem, Steven J. Schanz, Min Guo, Guo Feng Tian, Vaughn Washco, Nancy Stanwood, Matthew Rasband, Neeta Roy, Maiken Nedergaard, Leif A. Havton, Su Wang, Steven A. Goldman

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Congenitally hypomyelinated shiverer mice fail to generate compact myelin and die by 18-21 weeks of age. Using multifocal anterior and posterior fossa delivery of sorted fetal human glial progenitor cells into neonatal shiverer × rag2-/- mice, we achieved whole neuraxis myelination of the engrafted hosts, which in a significant fraction of cases rescued this otherwise lethal phenotype. The transplanted mice exhibited greatly prolonged survival with progressive resolution of their neurological deficits. Substantial myelination in multiple regions was accompanied by the acquisition of normal nodes of Ranvier and transcallosal conduction velocities, ultrastructurally normal and complete myelination of most axons, and a restoration of a substantially normal neurological phenotype. Notably, the resultant mice were cerebral chimeras, with murine gray matter but a predominantly human white matter glial composition. These data demonstrate that the neonatal transplantation of human glial progenitor cells can effectively treat disorders of congenital and perinatal hypomyelination.

Original languageEnglish (US)
Pages (from-to)553-565
Number of pages13
JournalCell Stem Cell
Volume2
Issue number6
DOIs
StatePublished - Jun 5 2008

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Neuroglia
Stem Cells
Ranvier's Nodes
Phenotype
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Myelin Sheath
Axons
Transplantation
Survival

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Neonatal Chimerization with Human Glial Progenitor Cells Can Both Remyelinate and Rescue the Otherwise Lethally Hypomyelinated Shiverer Mouse. / Windrem, Martha S.; Schanz, Steven J.; Guo, Min; Tian, Guo Feng; Washco, Vaughn; Stanwood, Nancy; Rasband, Matthew; Roy, Neeta; Nedergaard, Maiken; Havton, Leif A.; Wang, Su; Goldman, Steven A.

In: Cell Stem Cell, Vol. 2, No. 6, 05.06.2008, p. 553-565.

Research output: Contribution to journalArticle

Windrem, MS, Schanz, SJ, Guo, M, Tian, GF, Washco, V, Stanwood, N, Rasband, M, Roy, N, Nedergaard, M, Havton, LA, Wang, S & Goldman, SA 2008, 'Neonatal Chimerization with Human Glial Progenitor Cells Can Both Remyelinate and Rescue the Otherwise Lethally Hypomyelinated Shiverer Mouse', Cell Stem Cell, vol. 2, no. 6, pp. 553-565. https://doi.org/10.1016/j.stem.2008.03.020
Windrem, Martha S. ; Schanz, Steven J. ; Guo, Min ; Tian, Guo Feng ; Washco, Vaughn ; Stanwood, Nancy ; Rasband, Matthew ; Roy, Neeta ; Nedergaard, Maiken ; Havton, Leif A. ; Wang, Su ; Goldman, Steven A. / Neonatal Chimerization with Human Glial Progenitor Cells Can Both Remyelinate and Rescue the Otherwise Lethally Hypomyelinated Shiverer Mouse. In: Cell Stem Cell. 2008 ; Vol. 2, No. 6. pp. 553-565.
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