Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

Xu, Xiaoti; Wilschut, Karlijn J.; Kouklis, Gayle; Tian, Hua; Hesse, Robert; Garland, Catharine B.; Sbitany, Hani; Hansen, Scott L.; Seth, Rahul; Knott, P. Daniel; Hoffman, William Y.; Pomerantz, Jason H.

doi:10.1016/j.stemcr.2015.07.016

Cited by 117 publications

(105 citation statements)

References 40 publications

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“…NCAM is also expressed by human fetal muscle 27 and adult SCs 34 . We isolated HNK1 - NCAM + cells and evaluated their myogenic potential using two directed differentiation methods 10,11 .…”

Section: Resultsmentioning

confidence: 99%

ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs

et al. 2017

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Human pluripotent stem cells (hPSCs) can be directed to differentiate into skeletal muscle progenitor cells (SMPCs). However, the myogenicity of hPSC-SMPCs relative to human fetal or adult satellite cells remains unclear. HPSC-SMPCs derived by directed differentiation are less functional in vitro and in vivo compared to human satellite cells. Utilizing RNA-SEQ, we identified cell surface receptors ERBB3 and NGFR that demarcate myogenic populations, including PAX7 progenitors in human fetal development and hPSC-SMPCs. We demonstrated that hPSC skeletal muscle is immature, but inhibition of TGF-β signaling during differentiation improved fusion efficiency, ultrastructural organization, and expression of adult myosins. This enrichment and maturation strategy restored dystrophin in hundreds of dystrophin-deficient myofibers after engraftment of CRISPR/Cas9-corrected Duchenne muscular dystrophy hiPSC-SMPCs. The work provides an in-depth characterization of human myogenesis, and identifies candidates that improve the in vivo myogenic potential of hPSC-SMPCs to levels equal to directly-isolated human fetal muscle cells.

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Section: Resultsmentioning

confidence: 99%

ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs

et al. 2017

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“…In parallel, efforts to recapitulate niche characteristics in vitro by bioengineering methods and their cross-validation in vivo would advance our understanding of the microenvironment’s influence during satellite cell fate decisions [21]. Lastly, improved sorting strategies have made the study of cellular heterogeneity increasingly possible in human satellite cells [106,107] and would justify the clinical relevance of further study in this area.…”

Section: Discussionmentioning

confidence: 99%

Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis

Tierney

Sacco

2016

Trends in Cell Biology

130

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The cellular turnover required for skeletal muscle maintenance and repair is mediated by resident stem cells, also termed satellite cells. Satellite cells normally reside in a quiescent state, intermittently entering the cell cycle to fuse with neighboring myofibers and replenish the stem cell pool. However, the mechanisms by which satellite cells maintain the precise balance between self-renewal and differentiation necessary for long-term homeostasis remain unclear. Recent work has supported a previously unappreciated heterogeneity in the satellite cell compartment that may underlie the observed variability in cell fate and function. In this review, we examine the work supporting this notion as well as the potential governing principles, developmental origins, and principal determinants of satellite cell heterogeneity.

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“…The other human skeletal muscle derived stem cells have also been isolated and characterized, and their myogenic differentiation capacity examined in vivo [10–14]. In our method, the myogenic capacity in vivo was limited in the Sk-DN/29 + cells, a fraction suggested to mainly comprise satellite cells [16], and were eliminated during the first 3–4 weeks after transplantation in the present long-gap nerve niche ( S2 Fig ).…”

Section: Discussionmentioning

confidence: 99%

“…Human skeletal muscle-derived stem cells (Sk-SCs) have been isolated, characterized, and examined with respect to their in vivo differentiation capacities [10–14]. However, the therapeutic application of human Sk-SCs to nerve repair has never been investigated, even though they are thought to be involved in nerve regeneration [15].…”

Section: Introductionmentioning

confidence: 99%

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

et al. 2016

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Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8–12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk-SCs may be a practical source for autologous stem cell therapy following severe peripheral nerve injury.

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Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

Cited by 117 publications

References 40 publications

ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs

ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs

Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

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