Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nat Commun. 2021 Aug 18;12(1):5012. doi: 10.1038/s41467-021-25328-6.
Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in vertebrate embryos. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSC-derived tenocytes. We demonstrated that iPSC-tenocyte grafting contributed to motor function recovery after Achilles tendon injury in rats via engraftment and paracrine effects. The biomechanical strength of regenerated tendons was comparable to that of healthy tendons. We suggest that iPSC-tenocytes will provide a therapeutic option for tendon injury.
肌腱的自我更新很少发生，因为这种组织的血管化很差；因此，在严重损伤的情况下，通常采用自体肌腱的重建手术。然而，手术后的再损伤率相对较高，而且自体肌腱的采集会导致肌肉无力，从而延长康复时间。在这里，我们介绍一种基于诱导多能干细胞（iPSC）的技术，为肌腱损伤开发一种治疗选择。首先，我们通过重现在脊椎动物胚胎中逐步变窄的命运决定的正常过程，从人 iPSC 中获得肌腱细胞。我们使用单细胞 RNA 测序分析 iPSC 衍生的肌腱细胞的发育轨迹。我们证明，iPSC 衍生的肌腱细胞移植通过植入和旁分泌作用促进了大鼠跟腱损伤后的运动功能恢复。再生肌腱的生物力学强度与健康肌腱相当。我们认为 iPSC 衍生的肌腱细胞将为肌腱损伤提供一种治疗选择。
