In Vitro Induction of Tendon-Specific Markers in Tendon Cells, Adipose- and Bone Marrow-Derived Stem Cells is Dependent on TGF3, BMP-12 and Ascorbic Acid Stimulation
In Vitro Induction of Tendon-Specific Markers in Tendon Cells, Adipose- and Bone Marrow-Derived Stem Cells is Dependent on TGF3, BMP-12 and Ascorbic Acid Stimulation
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DOI：
10.3390/ijms20010149
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
de Girolamo, Laura
中科院分区：
文献类型：
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作者：
Orfei, Carlotta Perucca;Vigano, Marco;de Girolamo, Laura
间充质干细胞（MSC）和组织特异性祖细胞已被提出作为骨，软骨和肌腱相关病理再生医学方法的有用工具。细胞向所需的靶组织特异性谱系的分化在细胞疗法和组织工程的应用中已显示出优势。与成骨和成软骨分化不同，对于最佳的肌腱诱导方案没有共识。已经提出了许多生长因子用于此目的，包括BMP-12、b-FGF、TGF-3、CTGF、IGF-1和抗坏血酸（AA）。在这项研究中，这些生长因子的不同组合已经在两步分化方案的背景下进行了测试，以确定它们对脂肪组织和骨髓来源的MSC和肌腱细胞（TC）中肌腱标志物表达的诱导和维持的贡献。我们的研究结果表明，TGF-3是硬化的主要诱导剂，早期表达的肌腱标志物，而在同一时间抑制肌腱标志物正常表达后，如核心蛋白聚糖。相反，我们发现核心蛋白聚糖由BMP-12、b-FGF和AA诱导。我们的研究结果提供了新的见解不同的因素对间充质干细胞和TC的tenogenic诱导的影响，突出了TGF-3刺激的差异时机的重要性。
Mesenchymal Stem Cells (MSCs) and tissue-specific progenitors have been proposed as useful tools for regenerative medicine approaches in bone, cartilage and tendon-related pathologies. The differentiation of cells towards the desired, target tissue-specific lineage has demonstrated advantages in the application of cell therapies and tissue engineering. Unlike osteogenic and chondrogenic differentiation, there is no consensus on the best tenogenic induction protocol. Many growth factors have been proposed for this purpose, including BMP-12, b-FGF, TGF-3, CTGF, IGF-1 and ascorbic acid (AA). In this study, different combinations of these growth factors have been tested in the context of a two-step differentiation protocol, in order to define their contribution to the induction and maintenance of tendon marker expression in adipose tissue and bone marrow derived MSCs and tendon cells (TCs), respectively. Our results demonstrate that TGF-3 is the main inducer of scleraxis, an early expressed tendon marker, while at the same time inhibiting tendon markers normally expressed later, such as decorin. In contrast, we find that decorin is induced by BMP-12, b-FGF and AA. Our results provide new insights into the effect of different factors on the tenogenic induction of MSCs and TCs, highlighting the importance of differential timing in TGF-3 stimulation.