Chapter 16 Biological Therapies in Canine Sports Medicine 415by secreting cytokines, growth factors, and
extracellular matrix molecules that act either on
themselves (autocrine actions) or on neighbor‑
ing cells (paracrine actions) (Mei et al., 2017).
Given their ability to modulate host immune
responses, MSCs have been proposed as a
potential cellular therapy for autoimmune
disease such as rheumatoid arthritis. In the
treatment of OA, it has been suggested that
MSCs may have a positive effect via the secre‑
tion of bioactive trophic factors to exert potent
anti‑inflammatory and immunomodulatory
effects (Zhang et al., 2016).
Most likely MSCs repair tissue by multiple
interactions that include secretion of paracrine
factors to enhance regeneration of injured cells,
and stimulation of proliferation and differen‑
tiation of the stem‐like progenitor cells found
in most tissue. In the case of OA, for example,
MSC‐based treatments may enhance repair
and regeneration ability by the modulation
of the local T cell‐mediated immunological
response and by enhancing the potential for
tissue regeneration.
Osteoarthritis
Stem cell therapy is an emerging option for
OA treatment in dogs. The standard therapies
for OA involve palliation of pain using a
multimodal approach including NSAIDs,
analgesics, weight loss, exercise moderation,
and physical therapy. This approach offers
symptomatic relief in some cases, but pro‑
vides no disease‐modifying effect. The MSC‐
based treatment of OA aims at decreasing the
catabolic activity while enhancing cartilage
regeneration.
A recent experimental study using a canine
CCL transection model for developing OA
evaluated the synergistic effect of PRP and
adipose‐derived MSC in 24 Beagles (Yun et al.,
2016). The combination of PRP and MSCs is
attractive because PRP provides growth fac‑
tors and may enhance and promote cellular
engraftment, resulting in a synergistic effect.
The dogs were divided into four groups
treated with PRP, MSCs, a combination of PRP
and MSCs, and a control group with intra‐
articular saline injection. The animals were
treated with one injection per week for 4 weeks
and followed for 2 months. Outcomes included
lameness scoring for evaluating function and
focal compression strength, articular extracel‑
lular matrix compositions, histopathology,
and real‐time polymerase chain reaction (PCR)
for assessment of the treatment effect on carti‑
lage. Following treatment, the lameness scores
were significantly improved at 2 and 3 months
in the PRP and combined PRP and MSC
groups, but no difference was found between
PRP and MSC.
Naturally occurring hip OA has been the
focus of clinical trials using AD‐MSCs (Vilar
et al., 2013, 2014; Cuervo et al., 2014) and
stromal vascular fraction (Black et al., 2007;
Marx et al., 2014). One of the studies used
injection of MSCs at acupuncture points (Marx
et al., 2014), while the other studies delivered
MSCs intra‐articularly. These studies consist‑
ently showed improved outcomes in the dogs
treated with MSCs with no adverse effects
reported, providing preliminary evidence of a
biological effect of MSCs in dogs with OA.
Similar results were obtained in dogs with
elbow OA (Black et al., 2008; Guercio et al.,
2012). It is important to point out that force
plate analysis, considered the gold standard in
objective gait analysis, was performed in only
two of the available canine OA studies and
that a randomized design was applied in only
one study (Cuervo et al., 2014).
A prospective, randomized, masked, placebo‐
controlled, multicenter clinical trial investi‑
gated the effect of a single dose of allogeneic
AD‐MSCs, delivered intra‐articularly to either
one or two joints in 74 dogs (Harman et al.,
2016). The primary outcome measure was a
client‐based questionnaire, in addition to eval‑
uation by the veterinarian. AD‐MSC treatment
was shown to be safe and efficacious in com‑
parison to the placebo. AD‐MSC treatment
resulted in a significant improvement in client‐
and veterinarian‐based outcomes. Similar
results have been obtained by one author (AP)
in a prospective, randomized, double‐blind,
placebo‐controlled study investigating the
effect of allogeneic umbilical‐cord‐derived
MSCs as an intra‐articular treatment for elbow
OA (trial in progress). The group treated with
MSC experienced significantly more improve‑
ment in client‐based outcomes in comparison
to the group that received placebo.