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The Journal of Neuroscience, June 14, 2006, 26(24):6651-6660; doi:10.1523/JNEUROSCI.1007-06.2006

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Neurobiology of Disease
Skin-Derived Precursors Generate Myelinating Schwann Cells for the Injured and Dysmyelinated Nervous System

Ian A. McKenzie,^1,2,5 * Jeff Biernaskie,^1,2 * Jean G. Toma,^1,2 Rajiv Midha,⁶ and Freda D. Miller^1,2,3,4,5

Departments of ¹Developmental Biology and ²Brain and Behavior, Hospital For Sick Children Research Institute, Toronto, Ontario, Canada M5G 1X8, Departments of ³Physiology and ⁴Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8, ⁵Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4, and ⁶Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4

Correspondence should be addressed to Dr. Freda D. Miller, Developmental Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Email: fredam{at}sickkids.ca

Although neural stem cells hold considerable promise for treatment of the injured or degenerating nervous system, their current human sources are embryonic stem cells and fetally derived neural tissue. Here, we asked whether rodent and human skin-derived precursors (SKPs), neural crest-related precursors found in neonatal dermis, represent a source of functional, myelinating Schwann cells. Specifically, cultured SKPs responded to neural crest cues such as neuregulins to generate Schwann cells, and these Schwann cells proliferated and induced myelin proteins when in contact with sensory neuron axons in culture. Similar results were obtained in vivo; 6 weeks after transplantation of naive SKPs or SKP-derived Schwann cells into the injured peripheral nerve of wild-type or shiverer mutant mice (which are genetically deficient in myelin basic protein), the majority of SKP-derived cells had associated with and myelinated axons. Naive rodent or human SKPs also generated Schwann cells that myelinated CNS axons when transplanted into the dysmyelinated brain of neonatal shiverer mice. Thus, neonatal SKPs generate functional neural progeny in response to appropriate neural crest cues and, in so doing, provide a highly accessible source of myelinating cells for treatment of nervous system injury, congenital leukodystrophies, and dysmyelinating disorders.

Key words: neural crest; stem cells; dermis; nerve injury; shiverer mouse; cell transplantation

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Received March 7, 2006; revised May 4, 2006; accepted May 9, 2006.

Correspondence should be addressed to Dr. Freda D. Miller, Developmental Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Email: fredam{at}sickkids.ca

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