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

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 tran...

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Bibliographic Details
Published in:Experimental cell research 2004-07, Vol.297 (2), p.313-328
Main Authors: de la Fuente, Ricardo, Abad, José Luis, Garcı́a-Castro, Javier, Fernández-Miguel, Gemma, Petriz, Jordi, Rubio, Daniel, Vicario-Abejón, Carlos, Guillén, Pedro, González, Manuel A, Bernad, Antonio
Format: Article
Language:English
Subjects:
Adipocytes - cytology
Animals
Cartilage
Cartilage, Articular - cytology
Cell Differentiation
Cell Line
Cell Line, Tumor
Cell Lineage
Chondrocytes - cytology
Chondrocytes - physiology
Clone Cells
Dedifferentiated population
DNA - analysis
Endothelium, Vascular - cytology
Human articular chondrocytes
Humans
Immunohistochemistry
In vitro differentiation
Karyotyping
Kinetics
Mice
Multipotent population
Multipotent Stem Cells - cytology
Myoblasts - cytology
Neovascularization, Physiologic
Neurons - cytology
NIH 3T3 Cells
Recombinant Fusion Proteins - metabolism
RNA - analysis
Telomere
Teratocarcinoma - pathology
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Summary: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.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2004.02.026