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

Cell Stem Cell. 2008 Jun 5;2(6):553-65. doi: 10.1016/j.stem.2008.03.020.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism
  • Adult Stem Cells / transplantation*
  • Agenesis of Corpus Callosum
  • Animals
  • Animals, Newborn / abnormalities
  • Animals, Newborn / embryology
  • Cell- and Tissue-Based Therapy
  • Corpus Callosum / embryology
  • Corpus Callosum / metabolism
  • Corpus Callosum / transplantation*
  • Demyelinating Diseases / congenital
  • Demyelinating Diseases / therapy
  • Humans
  • Immunocompromised Host
  • Mice
  • Myelin Sheath / genetics
  • Myelin Sheath / metabolism*
  • Myelin Sheath / transplantation*
  • Neural Conduction
  • Neuroglia / metabolism
  • Neuroglia / transplantation*
  • Ranvier's Nodes / metabolism
  • Ranvier's Nodes / transplantation
  • Stem Cell Transplantation*
  • Tissue Distribution
  • Transplantation Chimera / embryology