Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells.
Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells.
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DOI：
10.3389/fvets.2015.00055
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发表时间：
2015
影响因子：
3.2
通讯作者：
Guest DJ
中科院分区：
文献类型：
--
作者：
Bavin EP;Smith O;Baird AE;Smith LC;Guest DJ
肌腱损伤通常发生在马和他们的修复通过疤痕组织的形成倾向于马的再损伤率高。多能干细胞可以提供细胞替代疗法，以改善肌腱组织再生并降低再损伤的频率。我们以前已经证明，马胚胎干细胞（ESC）分化成肌腱细胞谱系后，注射到受损的马肌腱，可以分化成功能性肌腱细胞在体外产生人工肌腱。诱导多能干细胞（iPSC）现在已经来自马，但迄今为止，还没有关于它们分化为肌腱细胞的能力的报道。由于iPSC可以从成体细胞类型中产生，因此它们提供了比ESC更容易获得的细胞来源，而ESC需要使用马胚胎。本研究的目的是比较通过两种独立方法产生的ESC和iPSC的肌腱分化。在二维分化试验中，iPSCs表达了肌腱相关基因和蛋白，这些基因和蛋白在转化生长因子β3的存在下得到了增强。然而，在三维（3D）分化试验中，iPSC未能分化为功能性肌腱细胞并生成人工肌腱。这些结果证明了3D体外肌腱测定用于测量肌腱分化的实用性，并且需要对马iPSC进行更详细的研究，以在其临床应用之前鉴定和理解其与多能ESC的表观遗传差异。
Tendon injuries occur commonly in horses and their repair through scar tissue formation predisposes horses to a high rate of re-injury. Pluripotent stem cells may provide a cell replacement therapy to improve tendon tissue regeneration and lower the frequency of re-injury. We have previously demonstrated that equine embryonic stem cells (ESCs) differentiate into the tendon cell lineage upon injection into the damaged horse tendon and can differentiate into functional tendon cells in vitro to generate artificial tendons. Induced pluripotent stem cells (iPSCs) have now been derived from horses but, to date, there are no reports on their ability to differentiate into tendon cells. As iPSCs can be produced from adult cell types, they provide a more accessible source of cells than ESCs, which require the use of horse embryos. The aim of this study was to compare tendon differentiation by ESCs and iPSCs produced through two independent methods. In two-dimensional differentiation assays, the iPSCs expressed tendon-associated genes and proteins, which were enhanced by the presence of transforming growth factor-β3. However, in three-dimensional (3D) differentiation assays, the iPSCs failed to differentiate into functional tendon cells and generate artificial tendons. These results demonstrate the utility of the 3D in vitro tendon assay for measuring tendon differentiation and the need for more detailed studies to be performed on equine iPSCs to identify and understand their epigenetic differences from pluripotent ESCs prior to their clinical application.