Title Direct Induction of Chondrogenic Cells from Human DermalFibroblast Culture by Defined Factors

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. Citation: Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, et al. (2013) Direct Induction of Chondrogenic Cells from Human Dermal Fibroblast Culture by Defined Factors. PLoS ONE 8(10): e77365. doi:10.1371/journal.pone.0077365 Editor: Dimas Tadeu Covas, University of Sao Paulo USP, Brazil Received February 20, 2013; Accepted September 2, 2013; Published October 16, 2013 Copyright: 2013 Outani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported in part by Scientific Research Grants Nos. 18390415, 19659378 and 21390421 from MEXT and the JST, CREST. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: ntsumaki@cira.kyoto-u.ac.jp