Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies—Proof of Concept

Abstract

Tendon and ligament injuries are frequent in sport horses and humans, and such injuries represent a significant therapeutic challenge. Tissue regeneration and function recovery are the paramount goals of tendon and ligament lesion management. Nowadays, several regenerative treatments are being developed, based on the use of stem cell and stem cell-based therapies. In the present study, the preparation of equine synovial membrane mesenchymal stem cells (eSM-MSCs) is described for clinical use, collection, transport, isolation, differentiation, characterization, and application. These cells are fibroblast-like and grow in clusters. They retain osteogenic, chondrogenic, and adipogenic differentiation potential. We present 16 clinical cases of tendonitis and desmitis, treated with allogenic eSM-MSCs and autologous serum, and we also include their evaluation, treatment, and follow-up. The concerns associated with the use of autologous serum as a vehicle are related to a reduced immunogenic response after the administration of this therapeutic combination, as well as the pro-regenerative effects from the growth factors and immunoglobulins that are part of its constitution. Most of the cases (14/16) healed in 30 days and presented good outcomes. Treatment of tendon and ligament lesions with a mixture of eSM-MSCs and autologous serum appears to be a promising clinical option for this category of lesions in equine patients.

Treatment of Equine Tarsus Long Medial Collateral Ligament Desmitis with Allogenic Synovial Membrane Mesenchymal Stem/Stromal Cells Enhanced by Umbilical Cord Mesenchymal Stem/Stromal Cell-Derived Conditioned Medium: Proof of Concept

“…The collected tissues were immersed in Dulbecco's phosphate-buffered saline (DPBS-14190-144, Gibco ® , Waltham, MA, USA) and transported to the laboratory facility, wrapped in ice packs to maintain refrigeration. These procedures have been previously described [28].…”

“…The collected synovial tissue was processed at the Laboratory of Veterinary Cell-based Therapies-ICBAS-UP, following the patented eSM-MSCs' isolation protocol (PCT/IB2019/052006, WO2019175773-"Compositions for use in the treatment of musculoskeletal conditions and methods for producing the same leveraging the synergistic activity of two different types of mesenchymal stromal/stem cells"-Regenera ® , Barcelona, Spain) previously described [28].…”

“…Additionally, the evaluation of these cells' secretome is important to understand their biological potential and their synergistic action, as MSCs isolated display similar appearances but different biological functions and markers depending on the their origins [27]. Equine SM-MSCs' tenogenic superiority presents them as good candidates for tendon and ligament regeneration [28][29][30]. Also, it has been proven that UC-MSCs present a superior ability in differentiating into tendon-like lineages and forming a tendon-like matrix, improving the regeneration of these structures [31].…”

Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy

“…Before the harvest, the owners signed an informed consent, and the animal underwent a complete medical and orthopedic evaluation, as well as a screening for infectious and contagious diseases. After harvesting the synovial membrane, cell isolation was performed as previously described ( 70 ). The applied therapeutic combination consisted of the administration of allogeneic cSM-MSCs suspended in autologous serum.…”

Advances in mesenchymal stem cells therapy for tendinopathies

“…Leal Reis et al. 36 used allogeneic MSCs to treat equine tendinopathy and obtained good histological results. Chong et al.…”