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Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice

Tendons are dense fibrous structures that attach muscles to bones. Healing of tendon injuries is a clinical challenge owing to poor regenerative potential and scarring. Here, we created reporter mice that express EGFP, driven by the promoter of the tendon-specific Scleraxis (Scx) transcription-facto...

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Autores principales: Komura, Shingo, Satake, Takashi, Goto, Atsushi, Aoki, Hitomi, Shibata, Hirofumi, Ito, Kenji, Hirakawa, Akihiro, Yamada, Yasuhiro, Akiyama, Haruhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055210/
https://www.ncbi.nlm.nih.gov/pubmed/32132649
http://dx.doi.org/10.1038/s41598-020-61063-6
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author Komura, Shingo
Satake, Takashi
Goto, Atsushi
Aoki, Hitomi
Shibata, Hirofumi
Ito, Kenji
Hirakawa, Akihiro
Yamada, Yasuhiro
Akiyama, Haruhiko
author_facet Komura, Shingo
Satake, Takashi
Goto, Atsushi
Aoki, Hitomi
Shibata, Hirofumi
Ito, Kenji
Hirakawa, Akihiro
Yamada, Yasuhiro
Akiyama, Haruhiko
author_sort Komura, Shingo
collection PubMed
description Tendons are dense fibrous structures that attach muscles to bones. Healing of tendon injuries is a clinical challenge owing to poor regenerative potential and scarring. Here, we created reporter mice that express EGFP, driven by the promoter of the tendon-specific Scleraxis (Scx) transcription-factor gene; we then generated induced pluripotent stem cells (iPSCs) from these mice. Utilising these fluorescently labelled iPSCs, we developed a tenogenic differentiation protocol. The iPSC-derived EGFP-positive cells exhibited elevated expression of tendon-specific genes, including Scx, Mohawk, Tenomodulin, and Fibromodulin, indicating that they have tenocyte-like properties. Finally, we demonstrated that these cells promoted tendon regeneration in mice after transplantation into injured tendons reducing scar formation via paracrine effect. Our data demonstrate that the tenogenic differentiation protocol successfully provided functional cells from iPSCs. We propose that pluripotent stem cell-based therapy using this protocol will provide an effective therapeutic approach for tendon injuries.
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spelling pubmed-70552102020-03-11 Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice Komura, Shingo Satake, Takashi Goto, Atsushi Aoki, Hitomi Shibata, Hirofumi Ito, Kenji Hirakawa, Akihiro Yamada, Yasuhiro Akiyama, Haruhiko Sci Rep Article Tendons are dense fibrous structures that attach muscles to bones. Healing of tendon injuries is a clinical challenge owing to poor regenerative potential and scarring. Here, we created reporter mice that express EGFP, driven by the promoter of the tendon-specific Scleraxis (Scx) transcription-factor gene; we then generated induced pluripotent stem cells (iPSCs) from these mice. Utilising these fluorescently labelled iPSCs, we developed a tenogenic differentiation protocol. The iPSC-derived EGFP-positive cells exhibited elevated expression of tendon-specific genes, including Scx, Mohawk, Tenomodulin, and Fibromodulin, indicating that they have tenocyte-like properties. Finally, we demonstrated that these cells promoted tendon regeneration in mice after transplantation into injured tendons reducing scar formation via paracrine effect. Our data demonstrate that the tenogenic differentiation protocol successfully provided functional cells from iPSCs. We propose that pluripotent stem cell-based therapy using this protocol will provide an effective therapeutic approach for tendon injuries. Nature Publishing Group UK 2020-03-04 /pmc/articles/PMC7055210/ /pubmed/32132649 http://dx.doi.org/10.1038/s41598-020-61063-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Komura, Shingo
Satake, Takashi
Goto, Atsushi
Aoki, Hitomi
Shibata, Hirofumi
Ito, Kenji
Hirakawa, Akihiro
Yamada, Yasuhiro
Akiyama, Haruhiko
Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
title Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
title_full Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
title_fullStr Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
title_full_unstemmed Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
title_short Induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
title_sort induced pluripotent stem cell-derived tenocyte-like cells promote the regeneration of injured tendons in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055210/
https://www.ncbi.nlm.nih.gov/pubmed/32132649
http://dx.doi.org/10.1038/s41598-020-61063-6
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