# 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

## TL;DR

This study shows that combining platelet-rich plasma with muscle-derived stem cells improves recovery in horses with tendon injuries, with added benefits from a second injection.

## Contribution

The study provides controlled evidence for the sequential use of PRP and autologous muscle-derived MSCs in equine tendon injuries.

## Key findings

- Horses treated with mdMSCs showed significant clinical and ultrasonographic improvement compared to placebo.
- A second injection of mdMSCs provided additional benefits in partial responders.
- No systemic adverse effects were observed, and local reactions were mild and transient.

## Abstract

Tendon and ligament injuries are common in sport horses and are associated with prolonged recovery and a high risk of recurrence. Orthobiologic therapies such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are increasingly used in clinical practice, but controlled data on autologous MSCs in naturally occurring lesions remain limited. In this randomized, double-blind, placebo-controlled clinical trial, horses with acute tendinopathies first received standardized leukocyte-reduced PRP. Animals that did not show sufficient clinical improvement were then randomized to receive intralesional autologous muscle-derived MSCs (mdMSCs) or placebo. To specifically assess the efficacy of mdMSCs beyond the initial PRP effect, analyses were performed in the per-protocol population excluding horses showing early clinical improvement after PRP. Horses treated with mdMSCs showed significant clinical and ultrasonographic improvement compared with placebo. A second injection in partial responders provided additional benefit. No systemic adverse effects were observed. These results support the clinical relevance of a sequential strategy combining immediate PRP treatment with delayed autologous cell therapy in equine tendon injuries.

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, n = 17) or placebo (n = 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.