title: WNT3A promotes myogenesis of human embryonic stem cells and enhances in vivo engraftment.
abstract: The ability of human embryonic stem cells (hESCs) to differentiate into skeletal muscle cells is an important criterion in using them as a cell source to ameliorate skeletal muscle impairments. However, differentiation of hESCs into skeletal muscle cells still remains a challenge, often requiring introduction of transgenes. Here, we describe the use of WNT3A protein to promote in vitro myogenic commitment of hESC-derived cells and their subsequent in vivo function. Our findings show that the presence of WNT3A in culture medium significantly promotes myogenic commitment of hESC-derived progenitors expressing a mesodermal marker, platelet-derived growth factor receptor-α (PDGFRA), as evident from the expression of myogenic markers, including DES, MYOG, MYH1, and MF20. In vivo transplantation of these committed cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice reveals survival and engraftment of the donor cells. The cells contributed to the regeneration of damaged muscle fibers and the satellite cell compartment. In lieu of the limited cell source for treating skeletal muscle defects, the hESC-derived PDGFRA(+) cells exhibit significant in vitro expansion while maintaining their myogenic potential. The results described in this study provide a proof-of-principle that myogenic progenitor cells with in vivo engraftment potential can be derived from hESCs without genetic manipulation.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Yongsung
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Suk
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Yu-Ru Vernon
authors.initials: YR
authors.lastname: Shih
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Seo
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Du
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Shyni
authors.initials: S
authors.lastname: Varghese
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D054715:Cardiotoxins / Q000633:toxicity; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D024510:Muscle Development / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D014183:Transplantation, Heterologous; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D054715:Cardiotoxins; C501641:MYH7 protein, human; C503799:MYOG protein, human; D018008:Myogenin; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D020796:Receptor, Platelet-Derived Growth Factor alpha; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
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