Mesenchymal stem cells (MSC) that can differentiate to various connective tissue cells may be useful for autologous cell transplantation to defects of bone, cartilage, and tendon, if MSC can be expanded in vitro. However, a short life span of MSC and a reduction in their differentiation potential in culture have limited their clinical application. The purpose of this study is to identify a growth factor(s) involved in self-renewal of MSC and the maintenance of their multilineage differentiation potential. Fibroblast growth factor-2 (FGF-2) markedly increased the growth rate and the life span of rabbit, canine, and human bone marrow MSC in monolayer cultures. This effect of FGF-2 was more prominent in low-density cultures than in high-density cultures. In addition, all MSC expanded in vitro with FGF-2, but not without FGF-2, differentiated to chondrocytes in pellet cultures. The FGF+ MSC also retained the osteogenic and adipogenic potential throughout many mitotic divisions. These findings suggest that FGFs play a crucial role in self-renewal of MSC.
We studied the biochemical characteristics of human knees with deficient anterior cruciate ligaments (ACL) and analysed their relationship to the time after ligamentous injury. Thirty-two patients with isolated ACLinjured knees and six healthy volunteers were enrolled. Synovial fluid samples were centrifuged after aspiration during arthroscopic examination, and aliquots of supernatant were frozen and stored at −80°C. The samples were analysed for interleukin (IL)-1β, tumour necrosis factor (TNF)-α, IL-6, matrix metalloproteinase (MMP)-3, and tissue inhibitor of metalloproteinase (TIMP)-1 using commercially available sandwich enzyme-linked immunosorbent assay. In fluid from ACL-injured knees, the average concentrations of IL-6, MMP-3 and TIMP-1 were highly elevated in comparison with normal controls. There was a statistically significant correlation between the concentrations of MMP-3 and IL-6. The IL-6 and TIMP-1 concentrations were interrelated. The concentration of MMP-3 remained high, independent of the duration since the injury, whereas the TIMP-1 and IL-6 levels decreased. The results suggest that the timing of the treatment of an ACL-injured knee might be of importance.Résumé Nous avons étudié les caractéristiques biochimiques des genoux humains avec un ligament croisé antérieur défectueux (LCA) et avons analysé leur rapport au temps après la lésion ligamentaire. Trente-deux malades avec une lésion isolée du LCA et six volontaires sains ont été enrôlés.
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