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Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture

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  • Taiki Nakajima

    (Center for iPS Cell Research and Application, Kyoto University)

  • Akihiro Nakahata

    (Graduate School of Medicine, Kyoto University)

  • Naoki Yamada

    (Center for iPS Cell Research and Application, Kyoto University
    Jikei University School of Medicine)

  • Keiko Yoshizawa

    (Center for iPS Cell Research and Application, Kyoto University)

  • Tomoaki M. Kato

    (Facility for iPS Cell Therapy, CiRA Foundation)

  • Mio Iwasaki

    (Center for iPS Cell Research and Application, Kyoto University)

  • Chengzhu Zhao

    (Center for iPS Cell Research and Application, Kyoto University)

  • Hiroshi Kuroki

    (Graduate School of Medicine, Kyoto University)

  • Makoto Ikeya

    (Center for iPS Cell Research and Application, Kyoto University)

Abstract

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.

Suggested Citation

  • Taiki Nakajima & Akihiro Nakahata & Naoki Yamada & Keiko Yoshizawa & Tomoaki M. Kato & Mio Iwasaki & Chengzhu Zhao & Hiroshi Kuroki & Makoto Ikeya, 2021. "Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25328-6
    DOI: 10.1038/s41467-021-25328-6
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    Cited by:

    1. Jingfei Xiong & Runxin Ma & Kun Xie & Ce Shan & Hanyi Chen & Yuqing Wang & Yuansong Liao & Yanhui Deng & Guogen Ye & Yifu Wang & Qing Zhu & Yunqiu Zhang & Haoyang Cai & Weihua Guo & Yike Yin & Zhongha, 2025. "Recapitulation of endochondral ossification by hPSC-derived SOX9+ sclerotomal progenitors," Nature Communications, Nature, vol. 16(1), pages 1-23, December.

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