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Human muscle-derived stem/progenitor cells promote functional murine peripheral nerve regeneration.

TitleHuman muscle-derived stem/progenitor cells promote functional murine peripheral nerve regeneration.
Publication TypeJournal Article
Year of Publication2014
AuthorsLavasani M, Thompson SD, Pollett JB, Usas A, Lu A, Stolz DB, Clark KA, Sun B, Péault B, Huard J
JournalJ Clin Invest
Volume124
Issue4
Pagination1745-56
Date Published2014 Apr 1
ISSN1558-8238
KeywordsAdult, Adult Stem Cells, Animals, Cell Differentiation, Disease Models, Animal, Heterografts, Humans, Mice, Muscle, Skeletal, Muscular Atrophy, Nerve Regeneration, Neural Stem Cells, Neuroglia, Neurons, Schwann Cells, Sciatic Nerve, Transcriptome, Young Adult
Abstract

Peripheral nerve injuries and neuropathies lead to profound functional deficits. Here, we have demonstrated that muscle-derived stem/progenitor cells (MDSPCs) isolated from adult human skeletal muscle (hMDSPCs) can adopt neuronal and glial phenotypes in vitro and ameliorate a critical-sized sciatic nerve injury and its associated defects in a murine model. Transplanted hMDSPCs surrounded the axonal growth cone, while hMDSPCs infiltrating the regenerating nerve differentiated into myelinating Schwann cells. Engraftment of hMDSPCs into the area of the damaged nerve promoted axonal regeneration, which led to functional recovery as measured by sustained gait improvement. Furthermore, no adverse effects were observed in these animals up to 18 months after transplantation. Following hMDSPC therapy, gastrocnemius muscles from mice exhibited substantially less muscle atrophy, an increase in muscle mass after denervation, and reorganization of motor endplates at the postsynaptic sites compared with those from PBS-treated mice. Evaluation of nerve defects in animals transplanted with vehicle-only or myoblast-like cells did not reveal histological or functional recovery. These data demonstrate the efficacy of hMDSPC-based therapy for peripheral nerve injury and suggest that hMDSPC transplantation has potential to be translated for use in human neuropathies.

DOI10.1172/JCI44071
Alternate JournalJ. Clin. Invest.
PubMed ID24642464
PubMed Central IDPMC3973076
Grant ListP30 AG024827 / AG / NIA NIH HHS / United States
R01 AR049684 / AR / NIAMS NIH HHS / United States
R21 NS081724-01 / NS / NINDS NIH HHS / United States
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