Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors

PLoS One. 2013 Oct 16;8(10):e77365. doi: 10.1371/journal.pone.0077365. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cartilage / cytology
  • Cartilage / metabolism
  • Cell Culture Techniques
  • Cell Transdifferentiation / genetics*
  • Chondrocytes / cytology*
  • Chondrocytes / metabolism*
  • Chondrogenesis / genetics
  • Collagen Type XI / genetics
  • Dermis / cytology*
  • Enhancer Elements, Genetic
  • Female
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism*
  • Gene Expression Profiling
  • Genetic Vectors / genetics
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Lentivirus / genetics
  • Mice
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transduction, Genetic

Substances

  • COL11A2 protein, human
  • Collagen Type XI
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Klf4 protein, rat
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins c-myc
  • SOX9 Transcription Factor

Grants and 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.