420 Canine Sports Medicine and Rehabilitation
restore motor function that is not under brain
control, but used alone are unlikely to restore
meaningful return of complex functions such as
balance or continence (Granger et al., 2012).
MSCs and neural crest stem cells are promis‑
ing cell types for treatment of SCI. Beneficial
effects include immunomodulation, regulation
of a regenerative permissive environment, pro‑
motion of axonal growth, and remyelination.
MSCs were shown to be safe and possibly benefi‑
cial in several canine SCI experimental and clini‑
cal studies (McMahill et al., 2015). Intraspinal
injections of various types of autologous and
allogenic MSCs in dogs with experimentally
induced SCI revealed that different MSC groups
showed significant improvements in locomotion
at 8 weeks after transplantation. This recovery
was accompanied by increased numbers of sur‑
viving neurons and neurofilament‐positive fibers
in the lesion site. Compared to controls, the lesion
sizes were smaller, and fewer microglia and reac‑
tive astrocytes were found in the spinal cord epi‑
center of all MSC groups. The data suggested
that transplantation of MSCs promotes func‑
tional recovery after SCI. Furthermore, applica‑
tion of umbilical cord‐derived MSCs led to more
nerve regeneration and neuroprotection and less
inflammation compared with other types of
MSCs (Ryu et al., 2012).
Percutaneous transplantation of human
umbilical cord‐derived MSCs has been reported
in a clinical case. In a paraplegic dog without
nociception, suspected to have fibrocartilagi‑
nous embolic myelopathy at the level of L3,
treatment resulted in restoration of ambulatory
function (Chung et al., 2013). However, the
dog did not regain nociception which raises
the possibility that the clinical improvement
was the result of activation of local spinal cir‑
cuitries and plasticity (spinal walking) and not
necessarily associated with treatment.
To summarize the status of spinal cord regen‑
eration in dogs, at the time of writing, clinical
applications of treatment protocols are not yet
available. Functional recovery after SCI is com‑
plex and dependent on the inherent plasticity
of the tissue and its responses and local envi‑
ronmental effects. It is likely that multimodal
efforts including differentiation of transplanted
cells into relevant cell types (neurons, glial
cells), regulation of scar formation, prevention
of cyst formation, and secretion of neurotrophic
and other factors to promote matrix repair and
regeneration are necessary to result in restora‑
tion of spinal cord function.Regulation of orthobiologics
Regulation of biological therapies is an impor‑
tant aspect of practicing regenerative medicine.
In the United States, the Center for Veterinary
Medicine (CVM) at the Food and Drug
Administration (FDA) is the regulatory body
overseeing the use of drugs. It is the authors’
understanding that most animal cell‐based
products, such as cultured stem cell therapies,
stromal vascular fraction, and, potentially, bone
marrow aspirate concentrate, are considered to
be drugs. It is less clear whether PRP, ACS, and
APS are considered to be drugs. It is also not
entirely clear what regulation exists for animal
cell‐based therapies. Presumably any animal
cell‐based therapies, if considered drugs, are
subject to existing regulation for animal drugs.
However, this is not entirely clear as the FDA
has also issued Guidance for Industry Cell‐Based
Products for Animal Use #218 that specifically
states that this document provides guidance
and does “not establish legally enforceable
responsibilities.” A full discussion regarding
the regulation and approval of regenerative
medicine therapies is beyond the scope of this
chapter. However, potential users of cell‐based
products are encouraged to educate themselves
on the regulatory process and the current status
of any products they intend to use and should
direct inquiries to the CVM at the FDA.References
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