title: Prospective heterotopic ossification progenitors in adult human skeletal muscle.
abstract: Skeletal muscle has strong regenerative capabilities. However, failed regeneration can lead to complications where aberrant tissue forms as is the case with heterotopic ossification (HO), in which chondrocytes, osteoblasts and white and brown adipocytes can arise following severe trauma. In humans, the various HO cell types likely originate from multipotent mesenchymal stromal cells (MSCs) in skeletal muscle, which have not been identified in humans until now. In the present study, adherent cells from freshly digested skeletal muscle tissue were expanded in defined culture medium and were FACS-enriched for the CD73(+)CD105(+)CD90(-) population, which displayed robust multilineage potential. Clonal differentiation assays confirmed that all three lineages originated from a single multipotent progenitor. In addition to differentiating into typical HO lineages, human muscle resident MSCs (hmrMSCs) also differentiated into brown adipocytes expressing uncoupling protein 1 (UCP1). Characterizing this novel multipotent hmrMSC population with a brown adipocyte differentiation capacity has enhanced our understanding of the contribution of non-myogenic progenitor cells to regeneration and aberrant tissue formation in human skeletal muscle.
authors.affiliation: CHUS Clinical Research Centre, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Downey
authors.affiliation: Shriners Hospital for Children, Montreal, QC, Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lauzier
authors.affiliation: Department of Orthopedic Surgery, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Kloen
authors.affiliation: CHUS Clinical Research Centre, Université de Sherbrooke, Sherbrooke, QC, Canada; Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Klaus
authors.initials: K
authors.lastname: Klarskov
authors.affiliation: CHUS Clinical Research Centre, Université de Sherbrooke, Sherbrooke, QC, Canada; Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Richter
authors.affiliation: Shriners Hospital for Children, Montreal, QC, Canada; Department of Surgery, Orthopedic Surgery Division, McGill University, Montreal, QC, Canada.
authors.forename: Reggie
authors.initials: R
authors.lastname: Hamdy
authors.affiliation: CHUS Clinical Research Centre, Université de Sherbrooke, Sherbrooke, QC, Canada; Department of Chemical and Biotechnological Engineering, Faculty of Engineering, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faucheux
authors.affiliation: Stem Cell Research Group, Faculty of Health, York University, Toronto, ON, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Scimè
authors.affiliation: CHUS Clinical Research Centre, Université de Sherbrooke, Sherbrooke, QC, Canada; Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Balg
authors.affiliation: CHUS Clinical Research Centre, Université de Sherbrooke, Sherbrooke, QC, Canada; Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address: guillaume.grenier@usherbrooke.ca.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Grenier
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology*; D009999:Ossification, Heterotopic / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*; D000071256:Uncoupling Protein 1
chemical_list: D015703:Antigens, CD; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1
keywords: Brown adipocytes; Heterotopic ossification; Human skeletal muscle; Mesenchymal stromal cells; Multilineage differentiation