Stepwise Differentiation of Human Embryonic Stem Cells Promotes Tendon Regeneration by Secreting Fetal Tendon Matrix and Differentiation Factors
Stepwise Differentiation of Human Embryonic Stem Cells Promotes Tendon Regeneration by Secreting Fetal Tendon Matrix and Differentiation Factors
复制标题
人胚胎干细胞逐步分化通过分泌胎儿肌腱基质和分化因子促进肌腱再生
DOI：
10.1002/stem.61
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发表时间：
2009-01-01
期刊：
影响因子：
5.2
通讯作者：
Ouyang, Hong Wei
中科院分区：
文献类型：
--
作者：
Chen, Xiao;Song, Xing-Hui;Ouyang, Hong Wei
人胚胎干细胞（hESCs）是组织再生的理想种子细胞，但尚未有关于其肌腱再生潜力的研究报道。本研究探讨了hESCs用于肌腱再生的策略和效果及其机制。hESCs首先被诱导分化为间充质干细胞（MSCs）， MSCs具有分化为三种间充质细胞系的潜力，并且MSC表面标记物呈阳性。hESC来源的MSCs （hESC - MSCs）在体外组织工程模型和体内异位肌腱再生模型中均能再生肌腱组织，这一结果被肌腱特异性基因和结构的表达所证实。在原位大鼠髌骨肌腱修复中，hESC-MSCs处理的肌腱具有比对照组更好的结构和力学性能。此外，hESC-MSCs在肌腱损伤部位至少可存活4周，并分泌人胎儿肌腱特异性基质成分和分化因子，从而激活肌腱的内源性再生过程。此外，所有样本均未发现畸胎瘤。这些发现证明了一种安全实用的应用ESCs进行肌腱再生的策略，并可能有助于未来治疗肌腱疾病的策略。干细胞2009；27:1276 - 1287
Human embryonic stem cells (hESCs) are ideal seed cells for tissue regeneration, but no research has yet been reported concerning their potential for tendon regeneration. This study investigated the strategy and efficacy of using hESCs for tendon regeneration as well as the mechanism involved. hESCs were first induced to differentiate into mesenchymal stem cells (MSCs), which had the potential to differentiate into the three mesenchymal lineages and were positive for MSC surface markers. hESC‐derived MSCs (hESC–MSCs) regenerated tendon tissues in both an in vitro tissue engineering model and an in vivo ectopic tendon regeneration model, as confirmed by the expression of tendon‐specific genes and structure. In in‐situ rat patellar tendon repair, tendon treated with hESC–MSCs had much better structural and mechanical properties than did controls. Furthermore, hESC–MSCs remained viable at the tendon wound site for at least 4 weeks and secreted human fetal tendon‐specific matrix components and differentiation factors, which then activated the endogenous regeneration process in tendon. Moreover, no teratoma was found in any samples. These findings demonstrate a safe and practical strategy of applying ESCs for tendon regeneration and may assist in future strategies to treat tendon diseases. STEM CELLS 2009;27:1276–1287