Dedifferentiated adult articular chondrocytes: a population of human multipotent primitive cells

Exp Cell Res. 2004 Jul 15;297(2):313-28. doi: 10.1016/j.yexcr.2004.02.026.

Abstract

Objective: To test the hypothesis that dedifferentiated adult human cartilage chondrocytes (HAC) are a true multipotent primitive population.

Methods: Studies to characterize dedifferentiated HAC included cell cycle and quiescence analysis, cell fusion, flow-FISH telomere length assays, and ABC transporter analysis. Dedifferentiated HAC were characterized by flow cytometry, in parallel with bone marrow mesenchymal stem cells (MSC) and processed lipoaspirate (PLA) cells. The in vitro differentiation potential of dedifferentiated HAC was studied by cell culture under several inducing conditions, in multiclonal and clonal cell populations.

Results: Long-term HAC cultures were chromosomically stable and maintained cell cycle dynamics while showing telomere shortening. The phenotype of dedifferentiated HAC was quite similar to that of human bone marrow MSC. In addition, this population expressed human embryonic stem cell markers. Multiclonal populations of dedifferentiated HAC differentiated to chondrogenic, osteogenic, adipogenic, myogenic, and neurogenic lineages. Following VEGF induction, dedifferentiated HAC expressed characteristics of endothelial cells, including AcLDL uptake. A total of 53 clonal populations of dedifferentiated HAC were efficiently expanded; 17 were able to differentiate to chondrogenic, osteogenic, and adipogenic lineages. No correlation was observed between telomere length or quiescent population and differentiation potential in the clones assayed.

Conclusion: Dedifferentiated HAC should be considered a human multipotent primitive population.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Animals
  • Cartilage, Articular / cytology
  • Cell Differentiation*
  • Cell Line
  • Cell Line, Tumor
  • Cell Lineage
  • Chondrocytes / cytology
  • Chondrocytes / physiology*
  • Clone Cells
  • DNA / analysis
  • Endothelium, Vascular / cytology
  • Humans
  • Immunohistochemistry
  • Karyotyping
  • Kinetics
  • Mice
  • Multipotent Stem Cells / cytology*
  • Myoblasts / cytology
  • NIH 3T3 Cells
  • Neovascularization, Physiologic
  • Neurons / cytology
  • RNA / analysis
  • Recombinant Fusion Proteins / metabolism
  • Telomere
  • Teratocarcinoma / pathology

Substances

  • Recombinant Fusion Proteins
  • RNA
  • DNA