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dc.contributor.authorZhang, Yuanfan
dc.contributor.authorKing, Oliver D.
dc.contributor.authorRahimov, Fedik
dc.contributor.authorJones, Takako I.
dc.contributor.authorWard, Christopher W.
dc.contributor.authorKerr, Jaclyn P.
dc.contributor.authorLiu, Naili
dc.contributor.authorEmerson, Charles P. Jr.
dc.contributor.authorKunkel, Louis M.
dc.contributor.authorPartridge, Terence A.
dc.contributor.authorWagner, Kathryn R.
dc.date2022-08-11T08:08:18.000
dc.date.accessioned2022-08-23T15:49:57Z
dc.date.available2022-08-23T15:49:57Z
dc.date.issued2014-06-15
dc.date.submitted2014-04-10
dc.identifier.citationZhang Y, King OD, Rahimov F, Jones TI, Ward CW, Kerr JP, Liu N, Emerson CP Jr, Kunkel LM, Partridge TA, Wagner KR. Human skeletal muscle xenograft as a new preclinical model for muscle disorders. Hum Mol Genet. 2014 Jun 15;23(12):3180-8. doi: 10.1093/hmg/ddu028. <a href="http://dx.doi.org/10.1093/hmg/ddu028">Link to article on publisher's site</a>
dc.identifier.issn0964-6906 (Linking)
dc.identifier.doi10.1093/hmg/ddu028
dc.identifier.pmid24452336
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28557
dc.description.abstractDevelopment of novel therapeutics requires good animal models of disease. Disorders for which good animal models do not exist have very few drugs in development or clinical trial. Even where there are accepted, albeit imperfect models, the leap from promising preclinical drug results to positive clinical trials commonly fails, including in disorders of skeletal muscle. The main alternative model for early drug development, tissue culture, lacks both the architecture and, usually, the metabolic fidelity of the normal tissue in vivo. Herein, we demonstrate the feasibility and validity of human to mouse xenografts as a preclinical model of myopathy. Human skeletal muscle biopsies transplanted into the anterior tibial compartment of the hindlimbs of NOD-Rag1null IL2rgammanull immunodeficient host mice regenerate new vascularized and innervated myofibers from human myogenic precursor cells. The grafts exhibit contractile and calcium release behavior, characteristic of functional muscle tissue. The validity of the human graft as a model of facioscapulohumeral muscular dystrophy is demonstrated in disease biomarker studies, showing that gene expression profiles of xenografts mirror those of the fresh donor biopsies. These findings illustrate the value of a new experimental model of muscle disease, the human muscle xenograft in mice, as a feasible and valid preclinical tool to better investigate the pathogenesis of human genetic myopathies and to more accurately predict their response to novel therapeutics.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24452336&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1093/hmg/ddu028
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectMolecular Biology
dc.subjectMolecular Genetics
dc.subjectMusculoskeletal Diseases
dc.subjectNervous System Diseases
dc.titleHuman skeletal muscle xenograft as a new preclinical model for muscle disorders
dc.typeJournal Article
dc.source.journaltitleHuman molecular genetics
dc.source.volume23
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/emerson/1
dc.identifier.contextkey5468148
html.description.abstract<p>Development of novel therapeutics requires good animal models of disease. Disorders for which good animal models do not exist have very few drugs in development or clinical trial. Even where there are accepted, albeit imperfect models, the leap from promising preclinical drug results to positive clinical trials commonly fails, including in disorders of skeletal muscle. The main alternative model for early drug development, tissue culture, lacks both the architecture and, usually, the metabolic fidelity of the normal tissue in vivo. Herein, we demonstrate the feasibility and validity of human to mouse xenografts as a preclinical model of myopathy. Human skeletal muscle biopsies transplanted into the anterior tibial compartment of the hindlimbs of NOD-Rag1null IL2rgammanull immunodeficient host mice regenerate new vascularized and innervated myofibers from human myogenic precursor cells. The grafts exhibit contractile and calcium release behavior, characteristic of functional muscle tissue. The validity of the human graft as a model of facioscapulohumeral muscular dystrophy is demonstrated in disease biomarker studies, showing that gene expression profiles of xenografts mirror those of the fresh donor biopsies. These findings illustrate the value of a new experimental model of muscle disease, the human muscle xenograft in mice, as a feasible and valid preclinical tool to better investigate the pathogenesis of human genetic myopathies and to more accurately predict their response to novel therapeutics.</p>
dc.identifier.submissionpathemerson/1
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.contributor.departmentWellstone Center for FSHD
dc.contributor.departmentEmerson Lab
dc.source.pages3180-8


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