Stem Cell Therapy for Canine Degenerative Joint Disease – a Review

The utilization of adipose-derived mesenchymal stem cell (AD-MSC) therapy for tissue regeneration and repair has been a rapidly growing area of scientific endeavour in both human and veterinary medicine over the past 10 years. It is anticipated that stem cell therapies will offer new medical applications across a wide spectrum of conditions, particularly in musculoskeletal, renal, cardiac immunologic and neurologic disorders; many academic institutions are working to define the properties of stem cells and to unlock their true medical potential (www.ukscf.org; www.stemcells.cam.ac.uk). One key area of interest is the immunomodulatory properties of MSCs which has given rise to human clinical trials of MSCs for Graft versus Host Disease (GvHD) (Yanez 2006, Le Blanc 2008) and MSCs have been demonstrated to reduce inflammation in a variety of clinical situations including: Crohn’s disease, autoimmune diseases, acute myocardial infarction (Barone 2013, Nauta 2007, Mei 2010) and osteoarthritis (Giordano 2007, Pockrop 2012).

In veterinary medicine, there is an increasing body of evidence supporting the efficacy of mesenchymal stem cell therapy in a variety of conditions. The benefits of stem cell treatment in the repair of tendon injuries in horses (Godwin 2011; Frisbie and Smith 2010; Smith et al 2013) is already widely accepted, with earlier research being further substantiated by data from the Royal Veterinary College, in which stem cell therapy is reported to have reduced the risk of re-injury by half when compared with conventional tendon treatments.

Two of the original key papers in canine osteoarthritis (OA) investigated the effects of intra-articular injection of elbow and hip OA with SVF (i.e. using stem cells from the stromal vascular fraction) in multi-centre, blinded clinical studies. These studies both demonstrated a significant reduction in pain and lameness in the treated dogs compared with the saline treated controls (Black 2007, Black 2008).

These findings are backed up by similar results from a study carried out at Monash Veterinary Hospital using adipose derived mesenchymal stem cells (AD-MSCs); dogs with moderate to severe OA of their stifles, elbows and/or hips showed significant improvement in lameness and quality of life (Ferguson 2012) when treated with stem cell therapy. Further small, well-controlled studies of elbow OA (Guercio 2012) and severe hip OA in a blinded force platform analysis (Vilar et al 2013) have also reported that dogs treated with AD-MSCs demonstrate significant improvements in their lameness scores.

Some particularly interesting evidence regarding the use of stem cells as an adjuvant to orthopaedic surgery in dogs comes from a double-blind, randomized clinical trial involving a total of 40 dogs (10 cases in each treatment arm) at the University of Minnesota. In this study 70% of dogs with elbow OA treated by proximal ulnar osteotomy plus adjuvant AD-MSCs showed significant improvement in all tested scores, including force platform analysis, compared with only 30% of dogs who had elbow surgery without stem cell therapy (Conzemius et al 2013; Kiefer et al 2013).

In 2014 a review by John Innes and Ben Walton (Veterinary Practice March 2014) presented the evidence and summarized current opportunities for the use of stem cell therapy in small animal orthopaedics – including ongoing research in bone healing and evidence of clinical efficacy in both human and veterinary non-union fractures – and concluded that the most promising application for stem cell therapy in small animal orthopaedics is for the treatment of joint disease.

More robust evidence is now starting to emerge from the many ongoing stem cell trials in humans and in dogs, with 2017 promising to be an interesting year as the data from these controlled studies starts to appear in the scientific press. The first of these, a randomised, placebo-controlled clinical study in moderate to severe canine OA was published in September 2016.  The attached paper by Robert Harman et al, describes the most significant study to date: a randomized, placebo-controlled, confirmatory study, designed to support a Market Authorization submission to the US Food and Drug Administration. This study has provided strong evidence of a significant clinical effect following a single injection of allogeneic, culture –expanded stem cells in moderate to severe canine OA ( Harman et al 2016). www.ncbi.nlm.nih.gov/pmc/articles/PMC5025432/