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

Taiki Nakajima (), Akihiro Nakahata, Naoki Yamada, Keiko Yoshizawa, Tomoaki M. Kato, Mio Iwasaki, Chengzhu Zhao, Hiroshi Kuroki and Makoto Ikeya ()
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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
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

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25328-6

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