title: Porcine skeletal muscle-derived multipotent PW1pos/Pax7neg interstitial cells: isolation, characterization, and long-term culture.
abstract: Developing effective strategies for the regeneration of solid tissue requires an understanding of the biology underlying the tissue's endogenous repair mechanisms. PW1/Peg3(pos)/Pax7(neg) skeletal muscle-derived interstitial progenitor cells (PICs) were first identified recently in the interstitium of murine skeletal muscle and shown to contribute to muscle fiber regeneration in vivo. PICs, therefore, represent a novel candidate resident progenitor cell for muscle regeneration. To explore the potential of these cells for clinical translation, we must ascertain the presence of PICs in larger mammalian species and identify criteria to successfully isolate and expand this population. In this study, we report the isolation, characterization, and maintenance of multipotent PICs from juvenile porcine skeletal muscle. We show that porcine PICs can be reproducibly isolated from skeletal muscle, express stem/progenitor cell markers, and have a stable phenotype and karyotype through multiple passages. Furthermore, porcine PICs are clonogenic and multipotent, giving rise to skeletal myoblast/myotubes, smooth muscle, and endothelial cells. In addition, PICs can be induced to differentiate into cardiomyocyte-like cells. These results demonstrate, in an animal model with size and physiology extrapolatable to the human, that porcine skeletal muscle-derived PW1(pos)/Pax7(neg) PICs are a source of stem/progenitor cells. These findings open new avenues for a variety of solid tissue engineering and regeneration using a single multipotent stem cell type isolated from an easily accessible source, such as skeletal muscle.
authors.affiliation: Centre of Human and Aerospace Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, School of Biomedical Sciences, King's College London, London, United Kingdom; Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool JM University, Liverpool, United Kingdom; Myology Group, Unité Mixte de Recherche S 787 INSERM, Université Paris VI/Pierre et Marie Curie, Paris, France.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Lewis
authors.affiliation: Centre of Human and Aerospace Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, School of Biomedical Sciences, King's College London, London, United Kingdom; Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool JM University, Liverpool, United Kingdom; Myology Group, Unité Mixte de Recherche S 787 INSERM, Université Paris VI/Pierre et Marie Curie, Paris, France.
authors.forename: Beverley J
authors.initials: BJ
authors.lastname: Henning
authors.affiliation: Centre of Human and Aerospace Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, School of Biomedical Sciences, King's College London, London, United Kingdom; Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool JM University, Liverpool, United Kingdom; Myology Group, Unité Mixte de Recherche S 787 INSERM, Université Paris VI/Pierre et Marie Curie, Paris, France.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Marazzi
authors.affiliation: Centre of Human and Aerospace Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, School of Biomedical Sciences, King's College London, London, United Kingdom; Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool JM University, Liverpool, United Kingdom; Myology Group, Unité Mixte de Recherche S 787 INSERM, Université Paris VI/Pierre et Marie Curie, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Sassoon
authors.affiliation: Centre of Human and Aerospace Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, School of Biomedical Sciences, King's College London, London, United Kingdom; Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool JM University, Liverpool, United Kingdom; Myology Group, Unité Mixte de Recherche S 787 INSERM, Université Paris VI/Pierre et Marie Curie, Paris, France georgina.ellison@kcl.ac.uk bernardo.nadalginard@kcl.ac.uk.
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Ellison
authors.affiliation: Centre of Human and Aerospace Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, School of Biomedical Sciences, King's College London, London, United Kingdom; Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool JM University, Liverpool, United Kingdom; Myology Group, Unité Mixte de Recherche S 787 INSERM, Université Paris VI/Pierre et Marie Curie, Paris, France georgina.ellison@kcl.ac.uk bernardo.nadalginard@kcl.ac.uk.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Nadal-Ginard
mesh_terms: D050156:Adipogenesis; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D059785:Karyotype; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000378:metabolism*; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D044968:Regenerative Medicine / Q000379:methods*; D013552:Swine; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D051741:Kruppel-Like Transcription Factors; D051763:PAX7 Transcription Factor; D017493:Leukocyte Common Antigens
keywords: Interstitial cells; Multipotent; PW1; Porcine; Skeletal muscle; Stem cells
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