西亚试剂：Neonatal Chimerization with Human Glial Progenitor Cells Ca

Neonatal Chimerization with Human Glial Progenitor Cells Can Both Remyelinate and Rescue the Otherwise Lethally Hypomyelinated Shiverer Mouse
Martha S. Windrem,1 Steven J. Schanz,1 Min Guo,1 Guo-Feng Tian,2 Vaughn Washco,1 Nancy Stanwood,3 Matthew Rasband,4 Neeta S. Roy,5 Maiken Nedergaard,2 Leif A. Havton,6 Su Wang,1 and Steven A. Goldman1,2,

1 Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
2 Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA
3 Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY 14642, USA
4 Department of Neurobiology, Baylor University College of Medicine, Houston, TX 77030, USA
5 Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10065, USA
6 Department of Neurology, UCLA Medical Center, Los Angeles, CA 90095, USA

Summary

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.

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