title: Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts.
abstract: BACKGROUND
  Studies of the pathogenic mechanisms underlying human myopathies and muscular dystrophies often require animal models, but models of some human diseases are not yet available. Methods to promote the engraftment and development of myogenic cells from individuals with such diseases in mice would accelerate such studies and also provide a useful tool for testing therapeutics. Here, we investigate the ability of immortalized human myogenic precursor cells (hMPCs) to form mature human myofibers following implantation into the hindlimbs of non-obese diabetic-Rag1 (null) IL2rγ (null) (NOD-Rag)-immunodeficient mice.
  
  
  RESULTS
  We report that hindlimbs of NOD-Rag mice that are X-irradiated, treated with cardiotoxin, and then injected with immortalized control hMPCs or hMPCs from an individual with facioscapulohumeral muscular dystrophy (FSHD) develop mature human myofibers. Furthermore, intermittent neuromuscular electrical stimulation (iNMES) of the peroneal nerve of the engrafted limb enhances the development of mature fibers in the grafts formed by both immortal cell lines. With control cells, iNMES increases the number and size of the human myofibers that form and promotes closer fiber-to-fiber packing. The human myofibers in the graft are innervated, fully differentiated, and minimally contaminated with murine myonuclei.
  
  
  CONCLUSIONS
  Our results indicate that control and FSHD human myofibers can form in mice engrafted with hMPCs and that iNMES enhances engraftment and subsequent development of mature human muscle.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201 USA.|Present address: FAME Laboratory, School of Exercise Science, University of Thessaly, Karies, Trikala, 42100 Greece.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Sakellariou
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201 USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201 USA.|Program in Molecular Medicine, University of Maryland, Baltimore, MD 21201 USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Mueller
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.|Present address: Berkeley Lights, Emeryville, CA 94608 USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Stadler
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201 USA.|Present address: Department of Health Care Sciences, Wayne State University, Detroit, MI 48201 USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Roche
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201 USA.|Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
authors.forename: Robert J
authors.identifier: 0000-0002-4933-3469
authors.initials: RJ
authors.lastname: Bloch
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004558:Electric Stimulation / Q000379:methods*; D006085:Graft Survival; D064593:Heterografts; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D024510:Muscle Development; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000378:metabolism / Q000473:pathology*; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D009469:Neuromuscular Junction; D010543:Peroneal Nerve; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: Desmin; Differentiation; FSHD; Lamin; Muscular dystrophy; Neuromuscular junction; Spectrin; Stem cell; Xenograft