In vivo cartilage formation from growth factor modulated articular chondrocytes.
Recent procedures for autologous repair of cartilage defects may be difficult in elderly patients because of the loss of stem cells and chondrocytes that occurs with age and the slow in vitro proliferation of chondrocytes from aged cartilage. In this study secondary chondroprogenitor cells were obtained by modulating the phenotype of articular chondrocytes with growth factors and stimulating the proliferation of these cells in culture. Chondrocytes isolated from the articular cartilage of mature New Zealand White rabbits were exposed to a combination of transforming growth factor beta and basic fibroblast growth factor treatment. These cells ceased the production of Collagen II (a marker for the chondrocyte phenotype) and underwent a 136-fold increase in cell number. Next, the cells were placed in high density culture and reexpressed the chondrocyte phenotype in vitro and formed hyaline cartilage in an in vivo assay. Primary chondrocytes obtained from articular cartilage of elderly humans could be manipulated in a similar fashion in vitro. These human secondary chondroprogenitor cells formed only cartilage tissue when assayed in vivo and in tissue bioreactors. This approach may be essential for autologous repair of degenerated articular cartilage in elderly patients with osteoarthritis.
Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
D M
DM
Bradham
W E
WE
Horton
D000368:Aged; D000818:Animals; D001672:Biocompatible Materials; D002358:Cartilage, Articular / Q000254:growth & development*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D003094:Collagen / Q000096:biosynthesis; D004338:Drug Combinations; D005109:Extracellular Matrix; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007797:Laminin; D051379:Mice; D008819:Mice, Nude; D011509:Proteoglycans; D011817:Rabbits; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen