Intra-articular Administration of Allogeneic Adipose Derived MSCs Reduces Pain and Lameness in Dogs With Hip Osteoarthritis: A Double Blinded, Randomized, Placebo Controlled Pilot Study

Abstract

This study was conducted to investigate the therapeutic effect of allogeneic adipose-derived MSCs on dogs with hip osteoarthritis (OA). Twenty dogs with bilateral osteoarthritis of the coxofemoral (hip) joint, diagnosed by a veterinarian through physical examination and radiographs were randomly allocated into four groups. Group 1 served as a placebo control and were injected with 0.9% sodium chloride (saline) (n = 4). Group 2 were injected with a single dose of 5 million MSCs (n = 5). Group 3 received a single dose of 25 million MSCs (n = 6) and Group 4 received a single dose of 50 million MSCs (n = 5). Intra-articular administration of allogeneic MSCs into multiple joints did not result in any serious adverse events. The average lameness score of the dogs in the placebo control group (−0.31) did not show improvement after 90 days of intra-articular saline administration. However, the average lameness score of the all MSC-treated dogs was improved 2.11 grade at this time point (P < 0.001). Overall, sixty five percent (65%) of the dogs that received various doses of MSCs showed improvement in lameness scores 90 days after intra-articular MSC administration. Our results showed that intra-articular administration of allogeneic adipose derived MSCs was well-tolerated and improved lameness scores and reduced pain in dogs associated with hip OA. All doses of MSCs were effective. Subsequent studies with more animals per group are needed to make a conclusion about the dose response. The improved lameness effect was present up to 90 days post-injection. Serum interleukin 10 was increased in a majority of the dogs that received MSCs and that also had improved lameness.

Platelet Lysate for Mesenchymal Stromal Cell Culture in the Canine and Equine Species: Analogous but Not the Same

“…The use of MSC in canine medicine is also becoming more popular. Canine MSC have been used successfully in several in vivo studies, especially for the treatment of osteoarthritis [ 8 , 9 , 10 ], but also for various other conditions such as atopic dermatitis [ 11 , 12 ], diabetes mellitus [ 13 ], inflammatory bowel disease [ 14 ], or to support neuroregeneration following vertebral compression fractures [ 15 ]. At the same time, there is a need to improve and harmonize canine MSC production processes.…”

Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration

“…Studies evaluating biosafety of allogeneic MSCs injections as an alternative to autologous injections have been published ( 4 – 8 ). Isolated and repeated injections of allogeneic MSCs in horses under several conditions ( 9 – 11 ) can generate positive results in different injuries and administration routes ( 12 – 14 ).…”

Manufacturing Mesenchymal Stromal Cells for the Treatment of Osteoarthritis in Canine Patients: Challenges and Recommendations

“…The clinical application of MSC-based therapy in veterinary medicine comprises of multiple target diseases, with the vast majority being focused on musculoskeletal conditions such as osteoarthritis (8,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), cruciate ligament disease (9,(35)(36)(37)(38), hip dysplasia (39), bone fractures and lesions (40,41), muscle tears (42,43) and tendinopathies (44,45). Canine clinical studies have also shown promising results for the treatment of diseases of the gastro-intestinal tract (46)(47)(48), central nervous system (49)(50)(51)(52)(53), cardiovascular system (54,55), cutaneous (56)(57)(58)(59) and ocular conditions (60)(61)(62)(63), resulting in encouraging safety and efficacy data (Figure 2).…”

“…In canine OA clinical studies, the characterization of MSCs immunophenotype is most often regarded as a routine protocol based on a minimal standardized conventional set of set of positive (CD44, CD29, CD90) and negative surface markers (CD34, CD45, MHC-II) (8,9,29,31,34). From this practical perspective, immunophenotyping is used to demonstrate the surface identity of the cells manufactured in different facilities worldwide, which however does not correlate with the functionality and therapeutic efficacy of the final product.…”