Chapter 16 Biological Therapies in Canine Sports Medicine 417ability to maintain viability and to proliferate after
transplantation, MSCs have immunosuppressive
properties and secrete growth/trophic factors that
support regenerative processes. The combination
of these properties makes MSCs highly suitable
for strategies to regenerate IVDs. Consequently,
a large body of in vitro studies and experimen‑
tal investigations based upon injury models in
laboratory animals has been accumulated in the
last decade with impressive results. An experi‑
mental study reported a significant delay in disc
degeneration in Beagles treated with MSC com‑
pared with the control group 12 weeks after injec‑
tion, as evaluated using MRI (Hiyama et al., 2008).
This work constitutes a valuable amount of
knowledge but still lacks the evidence that MSC
delivery is also successful in spontaneously occur‑
ring IVD degeneration.
Recently, human patients with lumbar IVDD
treated with intradiscal bone marrow‐derived
MSC injections reported diminished pain and
disability at the 12‐month follow‐up. The disc
water content on MRI was significantly ele‑
vated (Orozco et al., 2011). Another recent
human study documented an improvement
of one modified Pfirrmann grade (increased T2
signal of nucleus pulposus) along with clinical
improvement at the 1‐year follow‐up in 8/20
patients after percutaneous injection of MSCs
(Pettine et al., 2016). One conclusion from these
studies was that functional improvement of
patients was more evident than morphologi‑
cal improvement demonstrated by way of
MRI. Functional improvement was mainly
attributed to the immunomodulatory proper‑
ties of MSCs, leading to reduction of local
inflammation. However, based upon clinical
benefit and increased water signal on MRI
alone it cannot be stated that MSC treatment
is able to regenerate nucleus pulposus tissue.
Histological and immunophenotypic studies
would be necessary to determine survival,
proliferation, and differentiation of MSCs into
functional nucleus pulposus cells. To date,
only indirect methods are available to demon‑
strate effectiveness of the transplanted cells in
the clinical situation.
A first clinical canine study was recently
presented using a model of working German
Shepherd Dogs with spontaneously degener‑
ated lumbosacral discs that were treated with
intradiscal injections of autologous bone marrow‐
derived MSCs in combination with dorsal
laminectomy (Steffen et al., 2017) (Figure 16.8).(B)(A) (C)(D)Control MSCFigure 16.8 MRI of the lumbar spine in dogs treated with intradiscal injection of saline (control) and mesenchymal
stem cells (MSCs). The L6–L7 and L7–S1 intervertebral disc are shown on the left and right in each image, respectively.
(A) Preoperative and (B) postoperative MRI of the control dog. (C) Preoperative and (D) postoperative MRI of a dog
treated with MSCs. Note the progressive degeneration in the MSC‐treated dog compared to the unaltered degeneration
status in the control dog. The untreated L6–L7 discs in both dogs represent the signal behavior of healthy discs.