Harnessing the interplay between tendon stem/progenitor cell and microenvironment boosts tendon tissue regeneration

Tendon injuries are common musculoskeletal disorders characterized by limited natural healing capacity and inability to restore the original structure and function of tendons. Tendon tissue engineering based on tendon stem/progenitor cells (TSPCs) offers a potential strategy for tendon injury treatments. The function regulation of TSPCs is influenced by both in vivo and in vitro microenvironmental factors. Here, we provide a concise summary of the various subpopulations of TSPCs identified thus far. Additionally, we explore the current research progress on the in vivo microenvironment of TSPCs. Notably, we firstly introduce the concept of a "degeneration loop," which highlights the intricate interplay between the tendon microenvironment and TSPCs. Developing from this concept, we derive the theory and strategic framework of "Remodel niche - Disrupt Degeneration Loop - Tendon Healing" for effective tendon regeneration. Furthermore, we present an overview of the latest advances in the regulation of TSPCs expansion and differentiation through manipulation of the microenvironment in vitro and in vivo . Lastly, we address the challenges and related prospects encountered in the regenerative application of TSPCs subpopulations. A deeper multi-scale understanding of the interplay between distinct TSPCs subpopulations and their microenvironment will greatly contribute to the development of innovative tissue engineering strategies for successful tendon regeneration.