Transforming Growth Factor Beta3 Promotes Tendon Differentiation of Equine Embryo-Derived Stem Cells
Transforming Growth Factor Beta3 Promotes Tendon Differentiation of Equine Embryo-Derived Stem Cells
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DOI：
10.1089/ten.tea.2012.0372
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发表时间：
2013-10-01
影响因子：
4.1
通讯作者：
Guest, Debbie
中科院分区：
文献类型：
--
作者：
Barsby, Tom;Guest, Debbie
肌腱损伤经常发生在马身上，并且再生能力差，导致再损伤率高。马胚胎干细胞（ESCs）在受伤的马肌腱中大量存活，我们假设它们在体内分化为肌腱细胞。免疫细胞化学显示，在受伤的马肌腱中，胚胎干细胞表达肌腱祖细胞标记物硬细胞轴，并且损伤部位转化生长因子（TGF-）局部上调。本研究的目的是确定TGF-β信号转导是否能够通过ESC驱动腱细胞分化。暴露于体外分化的ESC的TGF-β在基因和蛋白质水平上产生了巩膜轴的上调，其中在TGF-β存在下产生的效果最大。TGF-3处理分化中的ESC也促进了其他肌腱相关基因和蛋白的显著上调，表明它可以促进ESC分化为肌腱细胞。我们的研究结果表明，马胚胎干细胞可以分化成治疗相关的细胞类型，TGF-β驱动的分化的胚胎干细胞可以提供一个模型，研究肌腱发育和更好地了解转录网络，参与马肌腱细胞分化从早期胚胎阶段。
Tendon injuries occur frequently in horses and have a poor capacity to regenerate, which leads to high re-injury rates. Equine embryo-derived stem cells (ESCs) survive in high numbers in the injured horse tendon and we hypothesized that they differentiate into tenocytes in vivo. Immunocytochemistry revealed that in the injured horse tendon ESCs express the tendon progenitor marker scleraxis and that there is a local upregulation of the transforming growth factor- (TGF-) at the injury site. The aim of this study was to determine if TGF- signaling was able to drive tenocyte differentiation by ESCs. Exposure of differentiating ESCs to TGF- in vitro produced an upregulation of scleraxis at the gene and protein level with the greatest effect being produced in the presence of TGF-3. TGF-3 treatment of differentiating ESCs also promotes a significant upregulation of other tendon-associated genes and proteins suggesting it can promote ESC differentiation into tenocytes. Our results demonstrate that equine ESCs can differentiate into a therapeutically relevant cell type and that TGF- driven differentiation of ESCs may provide a model to study tendon development and better understand the transcriptional networks that are involved in equine tendon cell differentiation from the early embryonic stages.