Disease-Modifying Medical and Cell-Based Therapy 381therapy for canine CR patients, although pre-
liminary information from the present authors’
laboratory did not suggest a treatment effect in a
small number of patients (unpublished studies).
Nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs
(NSAIDs) are considered a mainstay in the
treatment of pain associated with OA in dogs
(see Chapter 41). The degree to which NSAIDs
are able to decrease inflammation within the
stifle joint in dogs with CR is not known. A
recent study reported that CR dogs treated with
robenacoxib, a highly selective COX-2 inhibitor,
resulted in decreased C-reactive protein in
synovial fluid (Bennettet al. 2013). However, no
study has been published evaluating whether
use of NSAIDs has an effect on progression of
OA, the rate of contralateral rupture in dogs
with unilateral CR, or any other clinically rel-
evant marker of progressive cruciate ligament
fiber tearing.
Glucocorticoids
Glucocorticoids are potent anti-inflammatory
drugs used to treat a wide variety of inflam-
matory and autoimmune diseases in human
(Straub & Cutolo 2016) and veterinary patients
(Viviano 2013). In dogs with immune-mediated
inflammatory arthritis, the initial response
rate to glucocorticoids may be as high as 81%
(Clementset al. 2004). However, in addition to
polyuria, polydypsia and polyphagia, adverse
effects may include spontaneous tendon and
ligament rupture. Apoptosis, inhibition of cel-
lular proliferation, and a reduction in collagen
synthesis are likely important mechanisms
(Hossainet al. 2008). As a consequence of these
effects on collagen, tendon and ligament home-
ostasis, glucocorticoids are contraindicated as
a preventive or therapeutic modality for dogs
with CR.
Mesenchymal stem cells
A recent surge of interest has occurred in vet-
erinary medicine pertaining to the potential
for biological therapies, such as platelet-rich
plasma or mesenchymal stem cells (MSCs),
as potential regenerative or disease-modifying
treatments for a variety of orthopaedic condi-
tions. The potential for these therapies in dogs
with CR is only now beginning to be explored.
For a more in-depth review of platelet-rich
plasma, see Chapter 45.
MSCs have gained substantial interest as a
treatment modality for a wide variety of con-
ditions. The extent and mechanisms underly-
ing the regenerative and immune-modulating
capacity of MSCs are not fully understood,
although this field of scientific study is rapidly
evolving. With regards to the degenerative
and inflammatory arthropathy associated with
canine CR, the promise of autologous MSCs as
a disease-modifying therapy likely lies in their
immunomodulatory affects (Ghannam et al.
2010; Reinders et al. 2013). MSCs home to
damaged tissues and contribute to their repair
through a multitude of mechanisms, including
the secretion of growth factors, cytokines, anti-
fibrotic and angiogenic mediators, and extra-
cellular proteins (Djouadet al. 2009; Ghannam
et al. 2010). Immunomodulatory properties of
MSCs occur through suppression of immune
cells, being driven by effects on T-lymphocyte
function (Watermanet al. 2010), B-cell function
(Bouffiet al. 2010; Gonzalez-Reyet al. 2010), den-
dritic cell maturation, and macrophage pheno-
type (Kim & Hematti 2009); these properties
have the potential to influence arthritis sever-
ity (Kim & Hematti 2009). To date, only one
study has evaluated the potential for MSCs as
a disease-modifying therapy in dogs with CR
(Muiret al. 2016). This pilot study included 12
dogs with unilateral CR and a contralateral sta-
ble stifle with radiographic signs of effusion
and OA indicative of partial CR (see Chap-
ters 16 and 22). In this study, autologous bone
marrow-derived mesenchymal stem cells (BM-
MSCs) were cultured and subsequently injected
systemically and by intra-articular injection of
the partial CR stifle. The results showed that
the injection of autologous BM-MSCs in dogs
with partial CR suppressed systemic and sti-
fle joint inflammation, suggesting that such
treatment could ameliorate risk of contralateral
CR rupture through modification of the stifle
joint inflammatory response. In future studies,
this approach could be powered to determine
whether BM-MSC treatment could modify risk
of progressive fiber tearing and CR in at-risk
dogs (Muiret al. 2016).