Mesenchymal stromal cells effective in treating horse tendon injuries

A pilot study has found that multipotent mesenchymal stromal cells (MSCs) are effective in treating early-phase tendon disease in horses.

The researchers, reporting in the journal Cells, said their findings provide a basis for a larger controlled study.

Janina Burk and her fellow researchers said the treatment of tendon injuries in horses with MSCs was first described in the scientific literature nearly 20 years ago.

Since that pioneering case study, MSCs received tremendous attention in the equine community, with hopes that translation into human therapies could be facilitated based on experiences in equine medicine.

In the years that followed, large case studies were published with highly promising outcomes, albeit with historical or non-randomized controls, which were not directly comparable.

Furthermore, several studies were performed that focused on the treatment of experimentally induced equine tendon injuries with MSCs. Most reported improvements in the tendon structure and composition, but this could not be convincingly confirmed in other experimental studies.

Even today, it must be acknowledged that the clinical evidence of improved healing after local MSC treatment is still not sufficient, the study team said.

“The lack of a comprehensive clinical study on horses is due to the anticipated difficulties in the recruitment of suitable equine patients and compliant horse owners who agree to the blinded treatment and cope with the efforts associated with the follow-up.

“Nevertheless, this challenge has to be addressed to reach a satisfactory level of evidence for this MSC-based regenerative therapy.”

The study team performed a prospective, randomized, controlled, and triple-blind pilot study to gain insights into the effectiveness of MSC treatment and establish requirements for the design of a larger study that can finally provide evidence, with a simplified, efficient follow-up.

Fifteen horses with early naturally occurring tendon disease were recruited at three German veterinary teaching hospitals.

The horses were randomly assigned to one of two groups. One group received treatment which involved allogeneic fat-derived MSCs suspended in serum being injected into the tendon lesion. The other group received only serum injections into their tendon lesion.

The MSCs used were obtained from the fat tissue of a single healthy donor animal.

Dosage in each case was adapted to lesion size.

Standardized clinical examinations and diagnostic imaging were performed before treatment and six weeks after, as well as three, six, 12, and 18 months after treatment.

All horses were subjected to a controlled exercise program. The rate of re-injuries 12 months after treatment was chosen as the primary endpoint.

Veterinarians, examiners, and horse owners were blinded to the treatment group.

The study team found that clinical inflammation, lameness, and ultrasonography scores improved more over time in the MSC group.

“The lameness score difference significantly improved in the MSC group compared with the control group after six months,” they reported.

In the MSC group, five of the seven horses were free of re-injuries and still training after 12 months, and also after 18 months.

In the control group, three of the seven horses were still free of re-injury at the 12-month follow-up.

“These results suggest that MSCs are effective for the treatment of early-phase tendon disease and provide a basis for a larger controlled study,” the researchers concluded.

The study team, discussing their findings, said: “To the best of our knowledge, this is the first controlled study investigating the efficacy of allogeneic MSCs in naturally occurring tendon disease objectively and with long-term follow-up during rehabilitation training.

“Despite a relatively small number of cases included, our findings point to an improved clinical outcome after MSC treatment compared with serum treatment alone.”

Considering the possible mode of action of the MSC treatment of early tendon disease, the current findings, which include a reduction in clinical signs of inflammation, can be interpreted as long-term signs of an effective immunomodulatory action.

“The current pilot study consistently points to improved tendon healing after MSC treatment while using a randomized, controlled, and triple-blind study design for the first time in this context.

“The findings strongly encourage further advanced study while providing ideal prerequisites for such future work.”

The study team comprised Burk, with the University of Veterinary Medicine Vienna in Austria; Liza Wittenberg-Voges and Florian Geburek, with the University of Veterinary Medicine Hannover, Foundation, in Germany; Susanna Schubert, with the University of Leipzig Medical Center in Germany; and Carolin Horstmeier and Walter Brehm, with the University of Leipzig.

Burk, J.; Wittenberg-Voges, L.; Schubert, S.; Horstmeier, C.; Brehm, W.; Geburek, F. Treatment of Naturally Occurring Tendon Disease with Allogeneic Multipotent Mesenchymal Stromal Cells: A Randomized, Controlled, Triple-Blinded Pilot Study in Horses. Cells 2023, 12, 2513. https://doi.org/10.3390/cells12212513

The study, published under a Creative Commons License, can be read here.