Allogeneic Adipose-Derived Mesenchymal Stem Cells (Horse Allo 20) for the Treatment of Osteoarthritis-Associated Lameness in Horses: Characterization, Safety, and Efficacy of Intra-Articular Treatment

Abstract

Osteoarthritis commonly causes lameness in the horse and has a great impact in performance animals. Due to the limitations of current medical therapies, allogenic mesenchymal stem cells (MSCs) may become an alternative method to control inflammation, reduce tissue damage and pain, and therefore improve lameness. We present the results of a regulatory clinical trial testing adipose-derived MSCs (Horse Allo 20) in veterinary (Agencia Española del Medicamento y Productos Sanitarios, Spanish Medicines Agency, Reference number 325/ECV) involving a total number of 80 participants and with 90 days of follow-up period. The manufacturing process of Horse Allo 20 was robust with no influence of the adipose tissue donor (gender, age, or breed), sample origin (intraperitoneal or subcutaneous), or storage conditions (fresh vs. frozen product presentations) on the quality, safety, and efficacy of the drug product. An in vivo safety study showed that local and systemic tolerance was safe even after repeated intra-articular administration (three injections). An in vivo efficacy study demonstrated the efficacy of the treatment after one or two injections by a reduction in lameness (P < 0.05) for an extended period of time (90 days), decreasing the need for prolonged local and/or systemic anti-inflammatory therapies and their well-known deleterious effects and toxicities.

Single and repeated intra‐articular injections in the tarsocrural joint with allogeneic and autologous equine bone marrow‐derived mesenchymal stem cells are safe, but did not reduce acute inflammation in an experimental interleukin‐1β model of synovitis

“…A sustained monocytic inflammation has been found in previous studies of intra‐articular administration of BMDMSCs . This finding does not discount the significant clinical success that has been reported by others, as BMDMSCs mechanism of action is still largely unknown; anti‐inflammatory properties may not be what is responsible for clinical healing. In addition, the clinical effect of a transient monocytic inflammation is unknown.…”

“…Allogeneic stem cells have been evaluated alone and compared to autologous stem cells in vitro and in vivo in horses . These studies have yielded conflicting results.…”

“…Likewise, a single study of intravenous administration revealed an increase in CD8 + T cells following injection of allogeneic BMDMSCs, but no clinical effects . In fact, large clinical trials of intravenous and intra‐articular administration of allogeneic cells have demonstrated no adverse effects . One potential reason for conflicting results in small experimental studies may be the variability in individual horses' responses to any intra‐articular medication including the administration of MSCs .…”

Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes

“…It was reported that the reactivity of CD90 was 67.7% in umbilical cord-derived-MSCs [ 54 ], while more heterogeneous findings are available regarding the population of CD105-postivie cells among study groups; Barberini et al showed that adult MSCs from bone marrow, adipose tissue, and umbilical cord tissue was positive for CD105 [ 54 ], while other group reported that CD105 was not detectable in MSCs from bone marrow and adipose tissue [ 55 ]. Other study showed that adipose tissue-derived CD105 + MSCs were within the range of 21 to 74.4%, depending on the tissue sources (subcutaneous and intraperitoneal tissues) and passages [ 7 ]. Meanwhile, our results on the expression of CD29 and CD44 was comparable against other studies [ 55 , 56 ].…”

“…Thus, other alternatives, i.e., cellular therapies using autologous or allogenic origins are now being developed, mostly due to their biological characteristics and therapeutic potential for tissue regeneration [ 6 ]. Recently, Luis et al reported that repeated intra-articular injection of allogenic adipose-derived MSCs was able to reduce the lameness for 90 days, while reducing the administration of anti-inflammatory drugs [ 7 ]. Other study demonstrated that a combination of chondrogenic-induced MSCs and equine allogenic plasma led to an improvement of lameness score, lower glycosaminoglycan concentration and higher viscosity in synovial fluid in experimental groups [ 8 ].…”