Brown Jeffrey P, Galassi Thomas V, Stoppato Matteo, Schiele Nathan R, Kuo Catherine K
Department of Biomedical Engineering Tufts University, Science and Technology Center, 4 Colby Street , Medford, MA, 02155, USA.
Cell, Molecular & Developmental Biology Program Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA, 02111, USA.
Stem Cell Res Ther. 2015 May 9;6(1):89. doi: 10.1186/s13287-015-0043-z.
Advances in tendon engineering with mesenchymal stem cells (MSCs) are hindered by a need for cues to direct tenogenesis, and markers to assess tenogenic state. We examined the effects of factors involved in embryonic tendon development on adult MSCs, and compared MSC responses to that of embryonic tendon progenitor cells (TPCs), a model system of tenogenically differentiating cells.
Murine MSCs and TPCs subjected to cyclic tensile loading, transforming growth factor-β2 (TGFβ2), and fibroblast growth factor-4 (FGF4) in vitro were assessed for proliferation and mRNA levels of scleraxis, TGFβ2, tenomodulin, collagen type I and elastin.
Before treatment, scleraxis and elastin levels in MSCs were lower than in TPCs, while other tendon markers expressed at similar levels in MSCs as TPCs. TGFβ2 alone and combined with loading were tenogenic based on increased scleraxis levels in both MSCs and TPCs. Loading alone had minimal effect. FGF4 downregulated tendon marker levels in MSCs but not in TPCs. Select tendon markers were not consistently upregulated with scleraxis, demonstrating the importance of characterizing a profile of markers.
Similar responses as TPCs to specific treatments suggest MSCs have tenogenic potential. Potentially shared mechanisms of cell function between MSCs and TPCs should be investigated in longer term studies.
间充质干细胞（MSCs）在肌腱工程方面的进展受到指导肌腱生成的信号及评估肌腱生成状态的标志物的限制。我们研究了胚胎肌腱发育相关因子对成年间充质干细胞的影响，并将间充质干细胞的反应与肌腱生成分化细胞的模型系统——胚胎肌腱祖细胞（TPCs）进行了比较。
对体外施加循环拉伸负荷、转化生长因子-β2（TGFβ2）和成纤维细胞生长因子-4（FGF4）的小鼠间充质干细胞和肌腱祖细胞，评估其增殖情况以及硬骨素、TGFβ2、肌腱调节蛋白、I型胶原蛋白和弹性蛋白的mRNA水平。
在处理前，间充质干细胞中的硬骨素和弹性蛋白水平低于肌腱祖细胞，而其他肌腱标志物在间充质干细胞中的表达水平与肌腱祖细胞相似。单独使用TGFβ2以及与负荷联合使用时，基于间充质干细胞和肌腱祖细胞中硬骨素水平的升高，具有肌腱生成作用。单独负荷作用极小。FGF4下调了间充质干细胞中肌腱标志物的水平，但未下调肌腱祖细胞中的水平。特定的肌腱标志物并非始终随硬骨素上调，这表明表征标志物谱的重要性。
与肌腱祖细胞对特定处理的相似反应表明间充质干细胞具有肌腱生成潜力。在长期研究中应探究间充质干细胞和肌腱祖细胞之间潜在的细胞功能共享机制。
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