Perivascular-derived stem cells with neural crest characteristics are involved in tendon repair

Tendons and ligaments exhibit limited regenerative capacity following injury, with damaged tissue being replaced by a fibrotic scar. The physiological role of scar tissue is complex and has been studied extensively. In this study, we demonstrate that rat tendons contain a unique subpopulation of cells exhibiting stem cell characteristics, including clonogenicity, multipotency, and self-renewal capacity. Additionally, these putative stem cells expressed markers consistent with neural crest stem cells (NCSCs). Using immunofluorescent labeling, we identified P75(+) (p75 neurotrophin receptor) cells in the perivascular regions of the native rat tendon. Importantly, P75(+) cells were frequently localized near vascular cells and increased in number within the peritenon after injury. Ultrastructural analysis showed that perivascular cells detached from vessels in response to injury, migrated into the interstitial space, and deposited extracellular matrix. Characterization of P75(+) cells isolated from the scar tissue indicated that this population also expressed the NCSC markers, Vimentin, Sox10, and Snail. In conclusion, our results suggest that neural crest-like stem cells of perivascular origin reside within the rat peritenon and give rise to scar-forming stromal cells following tendon injury.