Chapter 16 Biological Therapies in Canine Sports Medicine 411severity of pathological changes in the CCL
based upon follow‐up arthroscopic assessment.
A third study was performed in which 24 dogs
had experimental transection of the CCL to
induce instability, lameness, and OA (Yun et al.,
2016). Dogs were randomized to receive sham
treatment, PRP, adipose‐derived mesenchymal
stem cells (MSCs), or PRP plus MSCs. Dogs
in the PRP group demonstrated significantly
greater improvement than sham‐treated dogs
based upon lameness scores. They also had sig‑
nificant improvement in comparison to saline‐
treated dogs based on mechanical testing of
articular cartilage, cartilage thickness, histology,
and biochemical composition of the cartilage.
The consistency of positive results from these
six prospective, randomized, blinded, and con‑
trolled studies are encouraging, suggesting that
intra‐articular PRP is beneficial in dogs. Three
of the studies included kinetic assessments of
weight bearing using force plate or pressure
mat data. All six studies demonstrated positive
effects on either subjective, objective, or both
types of outcome measures. However, there are
still notable limitations to the conclusions that
can be drawn. The conditions treated in each
study were different. Furthermore, three of the
studies were done in research dogs with experi‑
mentally induced pathological changes. This
latter point is particularly pertinent to the studies
involving dogs with induced CCL injury, which
differs from naturally occurring disease. There
are not yet any published studies evaluating
the use of PRP for managing naturally occur‑
ring partial CCL rupture. Finally, it should be
noted that the total number of dogs receiving
PRP in the six studies assessing intra‐articular
injection was just 48. As a result, there remains
a need for large (>50) randomized controlled
trials with kinetic (force plate or pressure mat)
data to assess the use of PRP in dogs with natu‑
rally occurring disease.
Other blood‐derived biological
treatments
Autologous conditioned serum
Autologous conditioned serum (ACS), also
known as interleukin receptor antagonist
protein (IRAP), is prepared by incubating whole
blood in a device with glass or borosilicate
beads at 37 °C for 7–24 hours. Leukocytes
adhere to the beads and are activated during
this incubation and can release high concen‑
trations of interleukin 1 receptor antagonist
(IL‐1ra). The blood is then centrifuged and the
serum fraction containing the high concentra‑
tion of IL‐1ra is collected for intra‐articular
injection in patients with OA. This is potentially
beneficial for patients with OA because IL‐1β is
the most important inflammatory cytokine in
the catabolic process of OA and cartilage
destruction. Blocking the effects of IL‐1β could
mitigate progression of this disease process.
Randomized studies in people and horses pro‑
vide variable evidence of efficacy with some
positive results (Frisbie, 2015). There are two
published studies in dogs demonstrating that
ACS in this species contains high concentra‑
tions of IL‐1ra, as well as increased concentra‑
tions of IL‐1β to some degree (Huggins et al.,
2015; Sawyere et al., 2016). However, there are
no studies at this time reporting the efficacy of
ACS for the treatment of OA in dogs.Autologous protein solutionAutologous protein solution (APS) is a blood‐
derived product that is similar to both PRP and
ACS. Blood is first processed in a commercial
device to make PRP. The PRP is transferred to
another device and filtered through polyacryla‑
mide beads, desiccating the PRP and providing
concentrated leukocyte, platelets, and plasma
proteins (Bertone et al., 2014). With human
blood this process results in the concentration
of anabolic and anti‐inflammatory cytokines
and lower concentrations of catabolic cytokines
(Woodell‐May et al., 2011). No studies have
assessed the cellular, growth factor, or cytokine
composition of APS made from the blood of
dogs. However, there has been one randomized,
controlled clinical trial of APS in horses and one
in dogs with OA of the stifle or elbow (Bertone
et al., 2014; Wanstrath et al., 2016). Results of the
canine study were mixed; dogs treated with
APS were significantly more lame 2 weeks fol‑
lowing injection based upon kinetic force plate
data but better at 12 weeks following injection.
Control dogs treated with saline did not show
any improvement based upon kinetic data.
Future studies will add to our understanding of
the utility of this biological treatment.