Bradham D M, Horton W E
Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Clin Orthop Relat Res. 1998 Jul(352):239-49.
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.
由于随着年龄增长干细胞和软骨细胞的丧失以及老年软骨中软骨细胞的体外增殖缓慢，近期用于软骨缺损自体修复的方法在老年患者中可能存在困难。在本研究中，通过用生长因子调节关节软骨细胞的表型并刺激这些细胞在培养中的增殖来获得二级软骨祖细胞。从成熟新西兰白兔的关节软骨中分离出的软骨细胞接受转化生长因子β和碱性成纤维细胞生长因子联合处理。这些细胞停止产生Ⅱ型胶原蛋白（软骨细胞表型的标志物），细胞数量增加了136倍。接下来，将这些细胞置于高密度培养中，在体外重新表达软骨细胞表型，并在体内试验中形成透明软骨。从老年人类关节软骨中获得的原代软骨细胞在体外也可以以类似方式进行处理。这些人类二级软骨祖细胞在体内和组织生物反应器中检测时仅形成软骨组织。这种方法对于骨关节炎老年患者退变关节软骨的自体修复可能至关重要。
