PhD Candidate The University of Hong Kong, Hong Kong
Abstract: Tendinopathy has a high prevalence in the elderly and athletes, with adverse effects due to slow and poor repair, affecting quality of life. Lgr5 and Lgr6 are markers for stem cells, and we have recently identified Lgr5+ cells in the developing knee joint and Achilles tendon. Expression of Lgr5 and Lgr6 in Achilles tendon development is dynamic. There are both Lgr5+ and Lgr6+ cells in early postnatal tendon. However, Lgr5+ cells are no longer detectable beyond 4 weeks of age, while Lgr6+ cells exist in adulthood, suggesting Lgr5+ cells are more relevant in development and growth. Tendon healing following injury or rupture decreases significantly with age that may correlate with low or absence of Lgr5+ cells. Thus, we propose that Lgr5+ progenitors are related to repair potential of tendons in young mice. Interestingly, we found that during healing of tendon injuries in adult mice, there is a sporadic reactivation of Lgr5-GFP+ cells, noted at 7 days post-surgery, underscoring a role of Lgr5+ cells in Achilles tendon repair. This led us to investigate the possible application of exogenous Lgr5+ cell as therapy in Achilles tendon repair. To assess the contribution of transplanted Lgr5+ cells to Achilles tendon repair following injury, we encapsulated Lgr5-GFP+ tdTomato+ cells isolated from E13.5 knee joint interzone in hydrogel, before implantation into the injury site. One week after surgery, exogenous Lgr5-GFP+ cells were found within the existing tendon, aligned parallel to the orientation of the collagen fibers, indicating engraftment of these cells that will contribute to the repair process. Additional works are needed to investigate the positive outcomes of such a therapeutic approach for tendinopathy.