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

Scientific Reports
Shingo KomuraHaruhiko Akiyama

Abstract

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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Citations

Sep 18, 2020·International Journal of Molecular Sciences·Maria Rita CiteroniBarbara Barboni
Nov 11, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Stephanie L TsaiJenna L Galloway
Dec 4, 2020·Development, Growth & Differentiation·Taiki Nakajima, Makoto Ikeya
Jul 11, 2021·Nature Communications·Deepak A KajiAlice H Huang
Jun 3, 2021·Tissue Engineering. Part B, Reviews·William H FangFinosh G Thankam

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Methods Mentioned

BETA
transgenic
PCR
Fluorescence
fluorescence-activated cell sorting
Flow cytometry
fluorescence microscopy
FACS

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