title: Transplanted mesoangioblasts require macrophage IL-10 for survival in a mouse model of muscle injury.
abstract: The aim of this study was to verify whether macrophages influence the fate of transplanted mesoangioblasts--vessel-associated myogenic precursors--in a model of sterile toxin-induced skeletal muscle injury. We have observed that in the absence of macrophages, transplanted mesoangioblasts do not yield novel fibers. Macrophages retrieved from skeletal muscles at various times after injury display features that resemble those of immunoregulatory macrophages. Indeed, they secrete IL-10 and express CD206 and CD163 membrane receptors and high amounts of arginase I. We have reconstituted the muscle-associated macrophage population by injecting polarized macrophages before mesoangioblast injection: alternatively activated, immunoregulatory macrophages only support mesoangioblast survival and function. This action depends on the secretion of IL-10 in the tissue. Our results reveal an unanticipated role for tissue macrophages in mesoangioblast function. Consequently, the treatment of muscle disorders with mesoangioblasts should take into consideration coexisting inflammatory pathways, whose activation may prove crucial for its success.
authors.affiliation: Division of Regenerative Medicine, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Bosurgi
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Corna
authors.forename: Michela
authors.initials: M
authors.lastname: Vezzoli
authors.forename: Thierry
authors.initials: T
authors.lastname: Touvier
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.forename: Silvia
authors.initials: S
authors.lastname: Brunelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002469:Cell Separation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000293:injuries*; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D016753:Interleukin-10