Although significant progress has been made recently, clinical data regarding the therapeutic efficacy of using stem cells to treat tendon injuries and diseases is limited. A recent systematic review [69] identified four clinical trials [70], [71], [72], [73] using BM- [71], [73] and allogenic adipose-derived stem cells [70], [72] for the treatment of tendon disorders (patellar tendinopathy, lateral epicondylar tendinopathy and rotator cuff tears). These four studies found that stem cell treatment led to improved tendon healing, as assessed by imaging, functional outcomes, and pain scores [70], [71], [72], [73]. However, only one trial had a control group [71], and all four studies were not blinded, allowing for a high risk of biased results. Therefore, the results should be interpreted with caution [69]. Clearly, many basic and translational studies are needed before stem cell-based therapies can be recommended as a routine clinical treatment for tendon injuries and diseases.
Furthermore, many challenging questions still remain to be addressed, such as: (1) Which sources of stem cells are most promising or bear the best potential to be used? (2) Are there subpopulations of cells among the heterogonous population of MSCs that may bring a more favourable outcome? (3) What type of injuries or diseases require the implantation of stem cells? (4) Can biologics such as stem cell-derived exosomes replicate the therapeutic effect of stem cells in tendon injury and/or disease, and to which extent? Moreover, as there are many significant biological differences between acute or chronic tendon injuries, and the repair mechanisms following these injuries [74], specific stem-cell therapy approaches may need to be tailored for each particular type of tendon injury.Research to address these questions and issues, may not only advance the basic understanding of the mechanisms underlying the roles stem cells play in tendon repair and regeneration but provide scientific merit and feasibility for stem cell-based approaches such as stem cell implantation, stem cell-derived biologics, and inducing endogenous stem homing. Finally, as a very critical step, it is important to establish standard methodologies and treatment protocols for harvesting, amplification, pretreatment, delivery, and postcell delivery treatment in preclinical studies and in clinical trials.