Chen Xiao, Song Xing-Hui, Yin Zi, Zou Xiao-Hui, Wang Lin-Lin, Hu Hu, Cao Tong, Zheng Minghao, Ouyang Hong Wei
Center for Stem Cells and Tissue Engineering, Institute of Cell Biology, School of Medicine, Zhejiang University, Hangzhou, China.
Stem Cells. 2009 Jun;27(6):1276-87. doi: 10.1002/stem.61.
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.
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。本研究调查了使用hESCs进行肌腱再生的策略和效果以及其中涉及的机制。首先将hESCs诱导分化为间充质干细胞（MSCs），后者具有分化为三个间充质谱系的潜力且对MSC表面标志物呈阳性。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再生出肌腱组织，这通过肌腱特异性基因的表达和结构得以证实。在大鼠原位髌腱修复中，用hESC-MSCs处理的肌腱在结构和力学性能方面比对照要好得多。此外，hESC-MSCs在肌腱伤口部位至少存活4周，并分泌人胎儿肌腱特异性基质成分和分化因子，进而激活肌腱中的内源性再生过程。而且，在任何样本中均未发现畸胎瘤。这些发现证明了应用ESCs进行肌腱再生的安全实用策略，并可能有助于未来治疗肌腱疾病的策略。
