title: Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts.
abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.
authors.affiliation: Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju, South Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Eom
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Mal Sook
authors.initials: MS
authors.lastname: Yang
authors.forename: In Keun
authors.initials: IK
authors.lastname: Jang
authors.forename: Hyo Eun
authors.initials: HE
authors.lastname: Kim
authors.forename: Doo Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Park
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kong
authors.forename: Kwang Yong
authors.initials: KY
authors.lastname: Shim
authors.forename: Jong In
authors.initials: JI
authors.lastname: Lee
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D002460:Cell Line; D019070:Cell Lineage; D018920:Coculture Techniques; D016189:Dystrophin / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D016189:Dystrophin; D018995:Myosin Heavy Chains