title: Fibrin gel improves the survival of transplanted myoblasts.
abstract: Duchenne muscular dystrophy (DMD) is the most frequent muscular dystrophy in children and young adults. Currently, there is no cure for the disease. The transplantation of healthy myoblasts is an experimental therapeutic strategy, since it could restore the expression of dystrophin  in DMD muscles. Nevertheless, this cellular therapy is limited by immune reaction, low migration of the implanted cells, and high early cell death that could be at least partially due to anoikis. To avoid the lack of attachment of the cells to an extracellular matrix after the transplantation,  which is the cause of anoikis, we tested the use of a fibrin gel for myoblast transplantation. In vitro, three concentrations of fibrinogen were compared (3, 20, and 50 mg/ml) to form a fibrin gel. A stiffer fibrin gel leads to less degradability and less proliferation of the cells. A concentration  of 3 mg/ml fibrin gel enhanced the differentiation of the myoblasts earlier as a culture in monolayer. Human myoblasts were also transplanted in muscles of Rag/mdx mice in a fibrin gel or in a saline solution (control). The use of 3 mg/ml fibrin gel for cell transplantation increased  not only the survival of the cells as measured after 5 days but also the number of fibers expressing dystrophin after 21 days, compared to the control. Moreover, the fibrin gel was also compared to a prosurvival cocktail. The survival of the myoblasts at 5 days was increased in both conditions  compared to the control but the efficacy of the prosurvival cocktail was not significantly higher than the fibrin gel.
authors.affiliation: Neurosciences Division-Human Genetics, CHUQ Research Centre-CHUL, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gerard
authors.forename: Marie Anne
authors.initials: MA
authors.lastname: Forest
authors.forename: Genevieve
authors.initials: G
authors.lastname: Beauregard
authors.forename: Daniel
authors.initials: D
authors.lastname: Skuk
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Tremblay
mesh_terms: D000328:Adult; D000818:Animals; D023102:Anoikis; D002448:Cell Adhesion; D049109:Cell Proliferation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D016189:Dystrophin / Q000096:biosynthesis; D005337:Fibrin; D005782:Gels; D006085:Graft Survival; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000628:therapy*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D055815:Young Adult
chemical_list: D016189:Dystrophin; D005782:Gels; D005337:Fibrin