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 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.


CONCLUSIONS
Dedifferentiated HAC should be considered a human multipotent primitive population.
de la Fuente
Ricardo
R
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Abad
José Luis
JL
García-Castro
Javier
J
Fernández-Miguel
Gemma
G
Petriz
Jordi
J
Rubio
Daniel
D
Vicario-Abejón
Carlos
C
Guillén
Pedro
P
González
Manuel A
MA
Bernad
Antonio
A
D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D002999:Clone Cells; D004247:DNA / Q000032:analysis; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D007700:Kinetics; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic; D009474:Neurons / Q000166:cytology; D012313:RNA / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016615:Telomere; D018243:Teratocarcinoma / Q000473:pathology
D011993:Recombinant Fusion Proteins; D012313:RNA; D004247:DNA