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

被引:72
作者
de la Fuente, R
Abad, JL
García-Castro, J
Fernández-Miguel, G
Petriz, J
Rubio, D
Vicario-Abejón, C
Guillén, P
González, MA
Bernad, A
机构
[1] CSIC, Dept Immunol & Oncol, Ctr Nacl Biotecnol, E-28049 Madrid, Spain
[2] UAM, Genetrix SL Fundac Pargue Cientif Madrid, Madrid, Spain
[3] Univ Barcelona, Lab Cryobiol, Hosp Clin, IDIBAPS, Barcelona, Spain
[4] CSIC, Ctr Invest Biol, Grp Growth Factors Vertebrate dev, Madrid, Spain
[5] Clin CEMTRO, Madrid, Spain
关键词
cartilage; human articular chondrocytes; dedifferentiated population; in vitro differentiation; multipotent population;
D O I
10.1016/j.yexcr.2004.02.026
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective. To test the hypothesis that dedifferentiated adult human cartilage chondrocytes (HAC) are a true multipotent primitive population. Methods. Studies to characterize dediffierentiated 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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:313 / 328
页数:16
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