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

Chad B Maki,Raymond Tong,Anthony Beck,Justin Choo,Fariborz Izadyar,Dori L Borjesson,Chan-Benami Cheuk Chi Wallis,Thomas Ramos

doi:10.3389/fvets.2020.00570

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.

Highlights

Osteoarthritis (OA) or degenerative joint disease (DJD) is the most common form of arthritis in dogs affecting a quarter of the population [1, 2]
Our double-blinded, placebo-controlled study clearly showed that a single intra-articular administration of allogeneic canine adipose derived Mesenchymal stem cell (MSC) improved the lameness score in dogs with chronic bilateral hip osteoarthritis
The effect was observed in some dogs as early as 5 days after IA administration of MSCs and it was prominent after 30 days of treatment and continued to improve lameness up to at least 90 days

Summary

Introduction

Osteoarthritis (OA) or degenerative joint disease (DJD) is the most common form of arthritis in dogs affecting a quarter of the population [1, 2]. In a small subset of dogs, OA occurs with no obvious primary causes and can be related to other contributing factors such as genetics, age, obesity, gender, exercise, and diet. It generally takes years of wear and tear before clinical symptoms of OA manifests, but in young patients with predisposing conditions such as hip dysplasia (HD) or elbow dysplasia (ED), symptoms may manifest as early as 1–2 years old [3, 4]. Utilization of anti-inflammatory cytokines for reducing joint pain and inflammation is reported. Among anti-inflammatory cytokines, it has been shown that IL4-10 fusion protein has chondroprotective, antiinflammatory, and potentially analgesic effects in the treatment of osteoarthritis [11]

Methods

Results

Conclusion