Imagine this clinical scenario: you are presented with a nine-year-old neutered female chocolate Labrador that has previously been diagnosed with osteoarthritis. The Labrador has been prescribed daily non-steroidal anti-inflammatory drugs (NSAIDs) alongside physical therapy; however, the owner reports difficulty with administering the daily NSAIDs, which has led to poor compliance. They ask you about potential alternative treatments.
You are aware that allogenic mesenchymal stem cell therapy is becoming increasingly popular. So you decide to consult the literature to explore whether intra-articular allogenic mesenchymal stem cell therapy is more effective at reducing lameness and pain in comparison with a placebo.
You review three prospective, double-blinded, placebo-controlled, randomised controlled trials. Sample sizes ranged from 20 to 93 dogs. Animals were a minimum of nine months old and weighed a minimum of 2.5kg. Females and males from small and large breeds were studied, and all dogs were client owned.
Two studies investigated the use of adipose-derived mesenchymal stem cells (Harman et al.,2016; Maki et al., 2020), whereas one study investigated use of umbilical-derived mesenchymal stem cells (Kim et al., 2019).
Owner- and veterinary-assessed outcomes were studied. Owner outcome measurements included:
- The Canine Brief Pain Inventory – changes in pain and lameness based on the owner’s perception and the client-specific outcome measure
- An evaluation of the impact of osteoarthritis on three owner-selected activities and how this changed with treatment
Outcome measurements included a veterinary pain score based on manipulation of the limb, veterinary assessment of clinical outcomes and veterinary pre- and post-lameness examinations
Veterinary outcome measurements included a veterinary pain score based on manipulation of the limb, veterinary assessment of clinical outcomes and veterinary pre- and post-lameness examinations, all of which were subjective measures.
Limitations of the evidence
One of the limitations of the evidence was the universally small sample size. A pilot study to calculate a power analysis was conducted by the authors of one paper (Kim et al., 2019). However, the paper’s clinical trial sample size was smaller than the one calculated, indicating a lack of power in the study.
The papers reviewed all used subjective primary measure outcomes, which have a high potential for bias, although this bias was mitigated by the use of two well-accepted subjective measures: the Canine Brief Pain Inventory and Hudson Visual Analog Scale scores.
All studied animals were taken home throughout the study, therefore there was a lack of environmental control. However, this provided an insight into how the animal coped within their usual environment.
Further, all three papers only assessed single-dose interventions. The longest period studied in any of the papers was six months (Kim et al., 2019). Therefore, any potential long-term adverse effects and the total duration of improvement of a single intra-articular injection of stem cells are unknown.
Additionally, there was a potential limitation caused by a conflict of interest in two of the papers (Harman et al., 2016; Kim et al., 2019). This was mitigated by a declaration of independence for the research of the remaining authors.
Summary of findings
All three papers showed significant improvements in the subjective measurements, while two studies indicated a statistically significant improvement in client and veterinary outcome measurements.
All three papers showed significant improvements in the subjective measurements, while two studies indicated a statistically significant improvement
Harman et al. (2016) reported statistically significant improvements in pain levels and a global score of clinical outcomes, both assessed by veterinary professionals. The study also found a statistically significant improvement in owner-specific outcome measurement.
Maki et al. (2020) found statistical improvement in lameness, as assessed by both owners and veterinary professionals.
Kim et al. (2019) found a statistically significant improvement in owner-reported pain levels and lameness. However, no statistically significant improvement was identified when considering subjective and objective veterinary measurements, including force plate gait analysis and veterinary orthopaedic examination.
Objective data outcomes and assessment by veterinary surgeons failed to find a significant improvement in peak vertebral force or lameness following intra-articular stem cell therapy compared to placebo.
There is moderate evidence from owner observation and veterinary assessment to suggest that intra-articular allogenic stem cell therapy (adipose- or umbilical-derived) has some efficacy for reducing pain and lameness compared to a placebo.
There is moderate evidence from owner observation and veterinary assessment to suggest that intra-articular allogenic stem cell therapy has some efficacy for reducing pain and lameness compared to a placebo
Beneficial further research should investigate: the use of intra-articular allogenic stem cells in comparison with conventional treatments such as intra-articular corticosteroid injections; safety in relation to multiple dosing of stem cells; and the most appropriate lineage and quantity of allogenic stem cells for the best clinical effect.
The application of evidence into practice should take into account multiple factors, not limited to individual clinical expertise, patient’s circumstances, owner’s values, the individual case in front of you, the availability of therapies and resources, and the country, location or clinic where you work.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.