The SA Journal Diabetes & Vascular Disease Vol 12 No 1 (July 2015)

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SA JOURNAL OF DIABETES & VASCULAR DISEASE REVIEW
VOLUME 12 NUMBER 1 • JULY 2015 17
interest in the potential utility of iPS cells in this regard. Potential
uses of iPS cells include: modelling neuropathic disease processes
in vitro; developing and screening candidate drugs that selectively
target diseased neuronal cells with particular genetic profiles; and
offering a novel paradigm of cell replacement therapy to support
neuronal regeneration.
The enormous potential utility of iPS cells for the treatment of
neuropathic pain is in its infancy and remains unsupported by an
evidence base. In addition to the limitations of iPS cells already
mentioned, a number of other problems would need to be
surmounted. For example, the retention of epigenetic profiles from
senescent cells may cause iPS cells, used for neuropathic pain disease
modelling or therapy, to lose their differentiated properties.
Conclusions
The evidence on the potential utility of cell therapies for the treatment
of neuropathic pain is predominantly based on research in animal
models on their efficacy and safety. The evidence suggests that
prima facie cell therapies reduce neuropathic pain and may modify
some of the cellular and molecular neuropathic pain mechanisms.
However, critical appraisal of the evidence thus far reveals it to be
far from conclusive and future research geared towards progression
on to clinical trials would need to address a number of issues. Firstly,
the preclinical evidence reported to date suggests that in vivo cell
therapies have a relatively short survival, which limits their clinical
utility in the treatment of chronic neuropathic pain. In this regard
future research on long-term graft viability is required.
Furthermore, prior to grafting, stem cells require expansion in
vitro and with increasing passaging time the stability of the cells
changes, which decreases the probability of them differentiating
into neurons.53 Accordingly, future research on the stability of cell
therapies intended for transplantation is required. The need for
future research on the issue of long-term stability and safety of cell
therapy is brought into even sharper focus by the observation that
following transplantation stem cell-derived grafts maintain a high
proliferative potential, which carries a significant oncogenic risk.54
This was highlighted by the first case report of a donor-derived
brain tumour following NSC transplantation.55
The evidence thus far on the potential disease-modifying
regenerative effects of cell therapies for the treatment of
neuropathic pain is limited to neuropathic conditions characterised
by focal nerve damage. Indeed, the mainstay of preclinical evidence
has used experimental animal models with limited focal nerve
damage. Future research would need to assess the potential utility
of cell therapies for more diffuse and widespread nerve damage,
for example in chemotherapy-induced polyneuropathy or diabetic
neuropathy, which are more common than focal neuropathies.
There may be a fourth dimension on the potential utility of cell
therapies for the treatment of neuropathic pain based on stem cell-
derived microvesicles. Research on the utility of stem cell-derived
microvesicles that carry miRNA, chemo-attractant, anti-apoptotic,
and anti-scarring factors are under investigation and early results have
demonstrated non-inferiority relative to cell therapies.56 However, the
evidence on stem cell-derived microvesicles is sparse; future research
on the role of stem cell-derived microvesicles is required.
In summary, cell therapies offer a novel curative therapeutic
dimension for the treatment of neuropathic pain. This is based on
replacing damaged neuronal tissue, protecting against progressive
nerve damage, and releasing paracrine and endocrine factors, which
repair the pathology that underlies the genesis and propagation of
damage within the somatosensory system.
Conflict of interest None
Funding sources None
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Key messages
• Cell therapies may offer palliative and curative potential in
diabetic neuropathy
• Stem cell treatments for neuropathic pain reverse and repair
the pathology that underlies the genesis and propagation of
damage within the somatosensory system
• Stem cell therapies can replace damaged neuronal tissue,
protect against progressive nerve damage, and release soluble
factors to facilitate neuronal repair