Adult tissue stem cells have shown promise for the treatment of debilitating tendon injuries. However, few comparisons of stem cells from different tissue sources have been made to determine the optimum stem cell source for treating tendon. Moreover, it is likely that the application of tenogenic growth factors will improve tendon stem cell treatments further, and a comprehensive comparison of a number of growth factors is needed. Thus far, different types of stem cells cannot be evaluated in a high-throughput manner. To this end, we have developed an approach to culture mesenchymal stem cells isolated from bone marrow in collagen type I hydrogels with tenogenic growth factors using economical, commercially available supplies. To optimize growth factors for this assay, FGF-2, TGF-β1, IGF-1, and/or BMP-12 were tested singly and in novel combinations of (1) BMP-12 and IGF-1, (2) TGF-β1 and IGF-1, and/or (3) BMP-12 and FGF-2 over 10 days. Our data suggest that BMP-12 supplementation alone results in the strongest expression of tendon marker genes, controlled contractility of constructs, a higher degree of cell alignment, and tendon-like tissue morphology. This easy-to-use benchtop assay can be used to screen novel sources of stem cells and cell lines for tissue engineering and tendon healing applications.

中文翻译：

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优化间充质干细胞三维培养中肌腱形成的生长因子诱导。

成人组织干细胞已显示出有望使肌腱衰弱的治疗方法。然而，很少有来自不同组织来源的干细胞的比较，以确定治疗肌腱的最佳干细胞来源。此外，使用腱生生长因子可能会进一步改善肌腱干细胞的治疗，因此需要对多种生长因子进行全面比较。迄今为止，不能以高通量的方式评估不同类型的干细胞。为此，我们已经开发出一种方法，可使用经济的，可商购的用品在具有肌腱生长因子的I型胶原水凝胶中培养从骨髓中分离的间充质干细胞。为了优化此测定法的生长因子，FGF-2，TGF-β1，IGF-1，和/或BMP-12分别以（1）BMP-12和IGF-1，（2）TGF-β1和IGF-1和/或（3）BMP-12和FGF-2的新颖组合进行了测试10天。我们的数据表明，单独补充BMP-12会导致肌腱标记基因的最强表达，可控制的构建体收缩力，更高的细胞排列度以及肌腱样组织形态。这种易于使用的台式测定法可用于筛选用于组织工程和肌腱愈合应用的干细胞和细胞系的新型来源。