title: Patient-tailored application for Duchene muscular dystrophy on mdx mice based induced mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) may be used as powerful tools for the repair and regeneration of damaged tissues. However, isolating tissue specific-derived MSCs may cause pain and increased infection rates in patients, and repetitive isolations may be required. To overcome these difficulties, we have examined alternative methods for MSC production. Here, we show that induced pluripotent stem cells (iPSCs) may be differentiated into mesenchymal stem cells (iMSCs) following exposure to SB431542. Purified iMSCs were administered to mdx mice to study skeletal muscle regeneration in a murine model of muscular dystrophy. Purified iMSCs displayed fibroblast-like morphology, formed three-dimensional spheroid structures, and expressed characteristic mesenchymal stem cell surface markers such as CD29, CD33, CD73, CD90, and CD105. Moreover, iMSCs were capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplanting iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowered oxidative damage as evidenced by a reduction in nitrotyrosine levels, and normal dystrophin expression levels were restored. This study demonstrates the therapeutic potential of purified iMSCs in skeletal muscle regeneration in mdx mice, and suggests that iPSCs are a viable alternate source for deriving MSCs as needed.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea; BK21 Plus Project, Yonsei University College of Dentistry, Seoul 120-752, South Korea. Electronic address: jmj1103@yuhs.ac.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea; Research Center for Radio-Senescence, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea.
authors.forename: Kyungshin
authors.initials: K
authors.lastname: Shin
authors.affiliation: National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea.
authors.forename: Seung Bum
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul 135-081, South Korea.
authors.forename: Dong Ryul
authors.initials: DR
authors.lastname: Lee
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea; Research Center for Radio-Senescence, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea. Electronic address: hck@kirams.re.kr.
authors.forename: Heechung
authors.initials: H
authors.lastname: Kwon
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation; D019070:Cell Lineage; D004149:Dioxoles / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D012038:Regeneration
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D015703:Antigens, CD; D001549:Benzamides; D004149:Dioxoles
keywords: Duchenne muscular dystrophy; Induced pluripotent stem cells; Mesenchymal stem cells; Regeneration; Skeletal muscle; Transplantation