Intra-articular Administration of Allogeneic Adipose Derived MSCs Reduces Pain and Lameness in Dogs with Hip Osteoarthritis: A Multicentered, Double Blinded, Randomized, Placebo Controlled Pilot Study
Presented by: Chad B. Maki
Authors: Chad Maki1 DVM; Anthony Beck3 DVM; Wallis Chan4 DVM; Justin Choo3 DVM, Thomas Ramos1 MS, MBA; Raymond Tong2 MD, Dori Borjesson5 DVM, PhD; Fariborz Izadyar1 DVM, PhD.
Affiliations: 1. VetCell Therapeutics, 2917 Daimler Street, Santa Ana CA 92705 2. VetCell Therapeutics Asia, Rm10-11, 10/F., Hollywood Plaza, 610, Nathan Road, Mong Kok, Hong Kong 3. Doctors Beck and Stone Clinic, Seaview Office, 92 Siena Ave, Discovery Bay, Hong Kong 4. Wellness Veterinary Hospital, 42-59 Tai Tong Road, Yuen Long, Hong Kong 5. Veterinary Institute for Regenerative Cures, UC Davis, School of Veterinary Medicine, 4325 Vet Med 3A Davis, CA 95616
Introduction: Recently the effect of allogeneic adipose derived MSCs for treatment of dog OA has been studied [Harman et al, 2016; Shah K, Zhao AG, Sumer H, 2018], and it was concluded that intra-articular administration of MSCs is safe and effectively reduces lameness and increases mobility as compared to the control group. However, in these studies all the dogs received a single dose of MSCs and the effect of various doses was not investigated. Also, the mechanism by which MSCs exert their therapeutic effect on reducing inflammation in arthritic joints has not been investigated. Therefore, this multicentered, randomized and double blinded pilot study was designed to better understand the effect of different doses of allogeneic adipose MSCs and their possible mode of action on improving lameness and mobility in dogs with OA.
Hypothesis / Objectives: This study was conducted to investigate the therapeutic effect of allogeneic canine adipose-derived MSCs (CAD-MSCs) on dogs with chronic hip osteoarthritis (OA).
Materials and Methods: Twenty dogs with bilateral osteoarthritis of the coxofemoral joint were randomly allocated in four groups. Group 1 served as placebo control (Sham) and injected with saline (n=4). Group 2 were injected with a single dose of 5 Million MSCs per joint (n=5). Group 3, 25 Million MSCS (n=6) and Group 4, 50 Million MSCs (n=5). Physical exam, lameness score, canine brief pain inventory (CBPI) and blood samples were taken at Day 0, 5, 30 and 90. Blood samples were tested for systemic cytokine levels.
Results: There were no serious adverse events reported. 63% of dogs treated with MSCs showed significant pain or interference reduction as compared to only 25% of placebo patients (p<0.005). The average lameness score of the dogs in placebo group did not show improvement after 30 or 90 days. However, the average lameness score of the MSC-treated dogs was improved at both time points. Overall, 78% of the dogs that received various doses of MSCs showed improvement in the lameness score at 90 days. Dogs with improved lameness in the placebo group and most MSC-treated dogs had an elevated serum IRAP at 30 days. None of the dogs in the placebo group that showed lameness improvement had elevated IL-10 in peripheral blood. However, about 70% of the dogs (4/6) with improved lameness that were treated with various doses of MSCs showed elevated serum IL-10. The level of serum IL-10 seems to correlate with the number of cells administered. However, due to a small sample size the difference was not significant (P=0.06).
Conclusions: Intra-articular administration of allogeneic CAD-MSCs was not associated with any serious adverse events and reduced pain and lameness in dogs with chronic bilateral hip OA. Our results showed that all doses of MSCs were effective, however there was a trend indicating that more cells resulted in more improvement. The improved lameness effect was present at least for 90 days. Serum levels of IL-10 only was increased in a majority of the dogs that received MSCs and also had improved lameness. Thus, IL-10 seems to be a good indicator of the lameness improvement due to cell therapy. All the dogs that showed improvement in their lameness score had an elevated serum level of IRAP, thus, the serum level of IRAP seems to be a good indicator of lameness improvement irrespective to treatment.
Acknowledgements, Funding, and Conflicts of Interest: Our gratitude goes to our team at VetCell Therapeutics USA™ and our VCT-Asia teams for cell line derivation and preparation and delivery of the therapeutic cells. We also thank Jason Pacchiarotti for compliance aspects of MSC manufacturing. We would like to thank Mr. Tom Yuen for his continuous support and inspiration. This study was funded by VetCell Therapeutics USA™. Chad Maki, Thomas Ramos and Fariborz Izadyar are employees of VetCell Therapeutics USA. Raymond Tong is an employee of VetCell Therepeutics Asia.