4. Discussion
inflammation, re-injuries, transient increase
INFLAMMATION, DISEASE
Here, the results of a randomized, controlled, triple-blind pilot study on MSC treatment of equine tendon disease are presented. 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.The MSCs used in the current study were obtained from the adipose tissue of a single healthy donor animal. Adipose tissue was chosen as an MSC source based on the previous experimental studies of our groups [The equine patients were enrolled in the study at three different university hospitals, to increase the chance of recruiting a sufficient number of suitable cases within a reasonable time frame. Treatment and follow-up were always performed according to standardized procedures and by veterinarians specifically trained for the study, to minimize variation between locations. However, despite defined inclusion criteria, the horses recruited and their tendon lesions were a source of variation and heterogeneity. While differences in the duration of symptoms and lesion size could be acknowledged through block randomization and by adapting the dosage, not all factors with potential impact on tendon healing could be leveled out actively. These include breed and intended use of the horse as well as the localization and extent of the tendon lesion within the metacarpal region. Furthermore, compliance with the rehabilitation training schedule was a subject of interrogation during the follow-up examinations but not specifically traceable. While these factors make the current study setting representative of clinical reality, they still represent a limitation of this study and likely contributed to the observed variation in the data.As in previous experimental trials [The clinical follow-up demonstrated that signs of inflammation were significantly decreased and weight bearing, i.e., the lameness score, improved 6 and 18 months after the injection of MSCs, whereas little to no improvement was observed in the control group. The imaging findings showed similar tendencies, with a significant improvement in the B-mode ultrasonography score. Moreover, fewer re-injuries occurred in the MSC group. However, when comparing the two groups based on the difference in the respective parameters over time, differences were only significant for the lameness score 6 months after treatment, which is likely due to the variation in the data and the limited number of equine patients included in the current pilot study.The improvement observed in tendon structure using B-mode ultrasonography corresponds to findings of previous experimental MSC studies with the treatment of collagenase-induced or naturally occurring tendon lesions [In this respect, it is important to attempt a comparison of the overall outcome, i.e., the re-injury rates, in the current study to previous clinical studies including larger cohorts but with historical or non-randomized controls instead of a randomized design [Considering the possible mode of action of the MSC treatment of early tendon disease [The early transient increase in blood perfusion and the long-term decrease in inflammation could provide a basis for improved tissue regeneration. In tendons, the latter strongly depends on the restoration of the extracellular matrix composition and architecture [