Influence of the growth factors PDGF-BB, TGF-beta1 and bFGF on the replicative aging of human articular chondrocytes during in vitro expansion.
Decreasing replicative potential and dedifferentiation of articular chondrocytes during expansion in cell culture are essential limitations for tissue engineering and cell therapy approaches. Telomeres and telomerase play a key role in cell development, aging, and tumorigenesis. There is evidence that growth factors are involved in regulating telomerase activity. Therefore, the objective was to evaluate the effect of selected growth factors on telomere biology of serially passaged chondrocytes. Human articular chondrocytes were isolated from cartilage of three patients undergoing total knee arthroplasty. The chondrocytes were cultured in monolayer with the growth factors PDGF-BB, TGF-beta1, and bFGF. Telomere length was measured by telomere restriction fragment length assay, and telomerase activity was determined by quantifying the gene expression of its catalytic subunit hTERT by rtPCR. Chondrocytes cultured with PDGF-BB and TGF-beta1 showed a significantly higher proliferation rate than control cells. None of the growth factor cultures revealed an accelerated rate of telomere shortening. Telomerase was not expressed in significant amounts in any of the chondrocyte cultures. Growth factor treatment of chondrocyte cell cultures for cell therapy purposes can be regarded as safe in terms of telomere biology.
Department of Trauma and Reconstructive Surgery, University of Regensburg, Franz-Josef-Strass-Allee 11, Regensburg 93042, Germany.
Anita
A
Brandl
Peter
P
Angele
Christina
C
Roll
Lucas
L
Prantl
Richard
R
Kujat
Bernd
B
Kinner
D000368:Aged; D000077214:Becaplermin; D002358:Cartilage, Articular / Q000166:cytology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012150:Polymorphism, Restriction Fragment Length; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D019098:Telomerase