title: Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors.
abstract: The repair of large cartilage defects with hyaline cartilage continues to be a challenging clinical issue. We recently reported that the forced expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) can induce chondrogenic cells from mouse dermal fibroblast culture without going through a pluripotent state. We here generated induced chondrogenic (iChon) cells from human dermal fibroblast (HDF) culture with the same factors. We developed a chondrocyte-specific COL11A2 promoter/enhancer lentiviral reporter vector to select iChon cells. The human iChon cells expressed marker genes for chondrocytes but not fibroblasts, and were derived from non-chondrogenic COL11A2-negative cells. The human iChon cells formed cartilage but not tumors in nude mice. This approach could lead to the preparation of cartilage directly from skin in human, without going through pluripotent stem cells.
authors.affiliation: Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan ; Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hidetatsu
authors.initials: H
authors.lastname: Outani
authors.forename: Minoru
authors.initials: M
authors.lastname: Okada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamashita
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tsumaki
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D018929:Cell Culture Techniques; D054338:Cell Transdifferentiation / Q000235:genetics*; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics; D024161:Collagen Type XI / Q000235:genetics; D020405:Dermis / Q000166:cytology*; D004742:Enhancer Elements, Genetic; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: C499319:COL11A2 protein, human; D024161:Collagen Type XI; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016271:Proto-Oncogene Proteins c-myc; D055758:SOX9 Transcription Factor