title: AG490 improves the survival of human myoblasts in vitro and in vivo.
abstract: Cell therapies consist in transplanting healthy cells into a disabled tissue with the goal to repopulate it and restore its function at least partially. In muscular diseases, most of the time, myoblasts are chosen for their expansion capacity in culture. Nevertheless, cell transplantation  has limitations, among them, death of the transplanted cells, during the days following the graft. One possibility to counteract this problem is to enhance the proliferation of the transplanted myoblasts before their fusion with the existing muscle fibers. AG490 is a specific inhibitor of  janus tyrosine kinase 2 (JAK2). The hypothesis is to block myoblast differentiation with AG490, thus permitting their proliferation. The inhibition of myoblast fusion by AG490 was confirmed in this study by gene expression and with a myosin heavy chain staining (MyHC). Moreover, cell survival  was estimated by flow cytometry. AG490 was found to protect myoblasts in vitro from apoptosis induced by H(2)O(2) or by preventing attachment of cells to their substrate. Finally, in an in vivo model of muscle regeneration, when AG490 was coinjected with the myoblasts their  survival was increased by 45% at 5 days after their transplantation.
authors.affiliation: Neurosciences Division-Human Genetics, CHUQ Research Centre-CHUL, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gérard
authors.forename: Christine
authors.initials: C
authors.lastname: Dufour
authors.forename: Sébastien
authors.initials: S
authors.lastname: Goudenege
authors.forename: Daniel
authors.initials: D
authors.lastname: Skuk
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D006861:Hydrogen Peroxide; D018995:Myosin Heavy Chains