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Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse.

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 x 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.

Pubmed ID: 18522848

Authors

  • Windrem MS
  • Schanz SJ
  • Guo M
  • Tian GF
  • Washco V
  • Stanwood N
  • Rasband M
  • Roy NS
  • Nedergaard M
  • Havton LA
  • Wang S
  • Goldman SA

Journal

Cell stem cell

Publication Data

June 5, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: R01 NS039559
  • Agency: NINDS NIH HHS, Id: R01 NS039559-09
  • Agency: NINDS NIH HHS, Id: R01NS039559

Mesh Terms

  • Adult Stem Cells
  • Agenesis of Corpus Callosum
  • Animals
  • Animals, Newborn
  • Cell- and Tissue-Based Therapy
  • Corpus Callosum
  • Demyelinating Diseases
  • Humans
  • Immunocompromised Host
  • Mice
  • Myelin Sheath
  • Neural Conduction
  • Neuroglia
  • Ranvier's Nodes
  • Stem Cell Transplantation
  • Tissue Distribution
  • Transplantation Chimera