Sequential Application of Autologous Platelet Rich Plasma and Muscle-Derived Mesenchymal Stem Cells for Acute Tendon Injuries in Horses: Early Clinical and Ultrasonographic Outcomes in a Randomized, Double-Blind Controlled Study

Tendon and ligament injuries are frequent in sport horses and are prone to recurrence due to incomplete healing. Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are increasingly used, but data controlled on the early effects of autologous MSCs remain limited. A prospective randomized, double-blind, placebo-controlled trial was conducted in horses with naturally occurring tendinopathies. After standardized PRP pretreatment, non-responders were randomized to receive intralesional autologous muscle-derived MSCs (mdMSCs, <i>n</i> = 17) or placebo (<i>n</i> = 6). Clinical and ultrasonographic parameters were evaluated at the recruitment period (T0) before the administration of the local treatment (T1), 4 (T2) and 8 weeks later (T3). Eighteen horses from both groups received at T2 a second intralesional injection of mdMSCs at the investigator's discretion; this phase was not randomized. Horses treated with mdMSCs showed significant improvements from T1 to T2 across both clinical and ultrasonographic parameters, whereas no significant changes were observed in the placebo group. Between-group comparison at T2 confirmed the significant superiority of mdMSCs. Further improvements were observed between T2 and T3 in the 18 horses that received a second injection. No systemic adverse events were recorded, and local reactions were mild and transient. This randomized controlled trial demonstrates early clinical and ultrasonographic efficacy of autologous mdMSCs in equine tendinopathy, with additional benefit from a second injection. The autologous approach combines efficacy and safety while avoiding the immunological and logistical constraints of allogeneic strategies.