title: The Development of Macrophage-Mediated Cell Therapy to Improve Skeletal Muscle Function after Injury.
abstract: Skeletal muscle regeneration following acute injury is a multi-step process involving complex changes in tissue microenvironment. Macrophages (MPs) are one of the key cell types involved in orchestration and modulation of the repair process. Multiple studies highlight the essential role of MPs in the control of the myogenic program and inflammatory response during skeletal muscle regeneration. A variety of MP phenotypes have been identified and characterized in vitro as well as in vivo. As such, MPs hold great promise for cell-based therapies in the field of regenerative medicine. In this study we used bone-marrow derived in vitro LPS/IFN-y-induced M1 MPs to enhance functional muscle recovery after tourniquet-induced ischemia/reperfusion injury (TK-I/R). We detected a 15% improvement in specific tension and force normalized to mass after M1 (LPS/IFN-γ) MP transplantation 24 hours post-reperfusion. Interestingly, we found that M0 bone marrow-derived unpolarized MPs significantly impaired muscle function highlighting the complexity of temporally coordinated skeletal muscle regenerative program. Furthermore, we show that delivery of M1 (LPS/IFN-γ) MPs early in regeneration accelerates myofiber repair, decreases fibrotic tissue deposition and increases whole muscle IGF-I expression.
authors.affiliation: Department of Kinesiology, The University of Texas at Austin, 1 University Station D3700, Austin, TX 78712, United States of America.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Rybalko
authors.affiliation: Department of Kinesiology, The University of Texas at Austin, 1 University Station D3700, Austin, TX 78712, United States of America.
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Hsieh
authors.affiliation: Department of Kinesiology, The University of Texas at Austin, 1 University Station D3700, Austin, TX 78712, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Merscham-Banda
authors.affiliation: Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, 107 W. Dean Keaton, Austin, TX 78712, United States of America.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Suggs
authors.affiliation: Department of Kinesiology, The University of Texas at Austin, 1 University Station D3700, Austin, TX 78712, United States of America.
authors.forename: Roger P
authors.initials: RP
authors.lastname: Farrar
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D016764:Cell Polarity / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D008297:Male; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000473:pathology; D013194:Staining and Labeling; D014945:Wound Healing / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens