Mesenchymal stromal cells for treatment of tendon injuries: first insights from a controlled, randomized, blinded veterinary patient study
Tendon injuries represent a challenge in orthopedics due to limited regeneration and frequentre-injuries. Treatment with multipotent mesenchymal stromal cells (MSC) is a promising therapy option in human as well as veterinary medicine, yet data from controlled trials are lacking. The aim of this study was to perform a first objective assessment of therapeutic efficacy in horses suffering from naturally occurring tendon disease under clinically relevant conditions.
Equine patients with (sub)acute injuries to their forelimb superficial digital flexor tendons were enrolled based on strict inclusion and exclusion criteria. Treatment groups were assigned by block randomization, and horses were treated intra-lesionally either with allogeneic MSC expanded under xeno-free culture conditions and suspended in equine serum, or with serum alone. MSC numbers and serum volume were adapted to the respective volume of the tendon lesion. Treatment and follow-up were performed according to standardized protocols and in a blinded manner, with clinical assessments, B-mode- and Doppler ultrasonography, and ultrasound tissue characterization (UTC) or magnetic resonance tomography at regular intervals. Fourteen patients completed their follow-up for at least 12 months, reaching the primary endpoint. The equine MSC expanded under xeno-free conditions were capable of differentiation into mesenchymal lineages, positive for CD29, CD44 and CD90 while lacking the defined exclusion marker antigens, and met the viability control criteria before delivery to the patients. All clinical parameters analyzed so far reveal a trend of better tendon healing in the MSCtreatment group. This includes clinically assessed scores as well as quantitative imaging results. Re-injuries until 12 months after treatment were more frequent in the control group (4 out of 7 patients) than in the MSC-treated group (2 out of 7 patients). While the final statistical analyses are pending, these results encourage further investigation and the study will provide a solid basis for larger controlled trials.