Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration
Mitra Lavasani, … , Bruno Péault, Johnny Huard
Mitra Lavasani, … , Bruno Péault, Johnny Huard
Published March 18, 2014
Citation Information: J Clin Invest. 2014;124(4):1745-1756. https://doi.org/10.1172/JCI44071.
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Research Article

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

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.

Authors

Mitra Lavasani, Seth D. Thompson, Jonathan B. Pollett, Arvydas Usas, Aiping Lu, Donna B. Stolz, Katherine A. Clark, Bin Sun, Bruno Péault, Johnny Huard

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Figure 6

hMDSPC transplantation improves functional recovery after sciatic nerve transection.

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hMDSPC transplantation improves functional recovery after sciatic nerve ...
Assessment of the functional recovery of regenerated sciatic nerve was performed using a walking track assessment. (A) Representative paw print patterns from mice transplanted with PBS, myoblasts, or hMDSPCs shown in consecutive weeks after implantation. Quantification of paw prints for (B) TS factor, (C) PL factor, and (D) SFI in hMDSPC-transplanted versus myoblast- and PBS-treated mice at consecutive weeks after denervation. Error bars indicate the mean ± SD. Plotted are average analyses of paw prints (4–5 paired paw prints/mouse) collected from PBS- (n = 20), myoblast- (n = 18), and hMDSPC-treated groups (n = 96 mice at 2 weeks, n = 96 mice at 4 weeks, n = 72 mice at 8 weeks, n = 72 mice at 12 weeks, and n = 48 mice at 14 weeks). *P < 0.05, comparing the individual hMDSPC populations isolated from individual donors 1–4 with PBS (Dunn’s test or Tukey’s test) or the three averaged populations of myoblasts (§P < 0.05, Dunn’s test). Comparison of PL factor from hMDSPCs isolated from donor 4 with that of the myoblast group at 2 weeks was not significant (NS, Dunn’s test).