title: Promotion of muscle regeneration by myoblast transplantation combined with the controlled and sustained release of bFGFcpr.
abstract: Although myoblast transplantation is an attractive method for muscle regeneration, its efficiency remains limited. The efficacy of myoblast transplantation in combination with the controlled and sustained delivery of basic fibroblast growth factor (bFGF) was investigated. Defects of thigh muscle in Sprague-Dawley (SD) rats were created, and GFP-positive myoblasts were subsequently transplanted. The rats were divided into three groups. In control group 1 (C1) only myoblasts were transplanted, while in control group 2 (C2) myoblasts were introduced along with empty gelatin hydrogel microspheres. In the experimental group (Ex), myoblasts were transplanted along with bFGF incorporated into gelatin hydrogel microspheres. Four weeks after transplantation, GFP-positive myoblasts were found to be integrated into the recipient muscle and to contribute to muscle fibre regeneration in all groups. A significantly higher expression level of GFP in the Ex group demonstrated that the survival rate of transplanted myoblasts in Ex was remarkably improved compared with that in C1 and C2. Furthermore, myofibre regeneration, characterized by centralization of the nuclei, was markedly accelerated in Ex. The expression level of CD31 in Ex was higher than that in both C1 and C2, but the differences were not statistically significant. A significantly higher expression level of Myogenin and a lower expression level of MyoD1 were both observed in Ex after 4 weeks, suggesting the promotion of differentiation to myotubes. Our findings suggest that the controlled and sustained release of bFGF from gelatin hydrogel microspheres improves the survival rate of transplanted myoblasts and promotes muscle regeneration by facilitating myogenesis rather than angiogenesis.
authors.affiliation: Department of Paediatric Surgery, Faculty of Medicine, University of Tsukuba, Japan.|Organoid Group, Biomaterial Centre, National Institute for Materials Science, Tsukuba, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Organoid Group, Biomaterial Centre, National Institute for Materials Science, Tsukuba, Japan.
authors.forename: Guoping
authors.initials: G
authors.lastname: Chen
authors.affiliation: Organoid Group, Biomaterial Centre, National Institute for Materials Science, Tsukuba, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawazoe
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Paediatric Surgery, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Komuro
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012038:Regeneration
chemical_list: D003692:Delayed-Action Preparations; D018006:Myogenic Regulatory Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C485184:enhanced green fluorescent protein; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins
keywords: MyoD1; angiogenesis; basic FGF; gelatin hydrogel; muscle regeneration; myoblast transplantation; myogenin