Biomedical Engineering Reference
In-Depth Information
Injury
http://dx.doi.org/10.5772/58906
Most SHEDs and DPSCs express a set of adult bone marrow stromal stem cell (BMSC) markers
(CD90, CD73, and CD105), neural stem/progenitor cell markers (Doublecortin, GFAP, and
Nestin), and early neuronal and oligodendrocyte markers (βIII-tubulin, A2B5 and CNPase),
but not markers for mature oligodendrocytes (MBP and APC) (Sakai et al., 2012). Since
naturally exfoliated deciduous and impacted adult wisdom teeth are dispensable, DPSCs and
SHEDs can be easily obtained by utilizing a simple protocol (Liu et al., 2006). DPSCs and
SHEDs exhibit a faster rate of proliferation and a higher number of population doublings in
vitro, compared with BMSCs. Furthermore, the rate SHEDs is 1.5 times faster than that of
DPSCs (Miura et al., 2003). Like BMSCs, they are multipotent cells that can differentiate in vitro
into a variety of cell types including odontoblasts, osteoblasts, chondrocytes, adipocytes,
endothelial cells, myocytes, and functionally active neurons (Gronthos et al., 2000, Gronthos
et al., 2002a, Batouli et al., 2003, Miura et al., 2003, Nosrat et al., 2004, Kerkis et al., 2006,
d'Aquino et al., 2007, Arthur et al., 2008, Arminan et al., 2009, Wang et al., 2010). Furthermore,
when transplanted into the transected spinal cord (SC), they specifically differentiate toward
mature oligodendrocyte lineages (Sakai et al., 2012: see below).
A cDNA microarray analysis showed that SHEDs express many genes encoding extracellular
and cell-surface proteins at levels at least two-fold higher than are expressed in BMSCs (Sakai
et al., 2012). It has been shown that the array of trophic factors produced by engrafted DPSCs
and SHEDs provide significant therapeutic benefits for the treatment of preclinical animal
disease models, including myocardial infarction, systemic lupus erythematosus (SLE),
ischemic brain injury, SCI, and colitis (Gandia et al., 2008, Nakashima et al., 2009, Yamaza et
al., 2010, de Almeida et al., 2011, Leong et al., 2012, Ma et al., 2012, Sakai et al., 2012, Taghipour
et al., 2012, Zhao et al., 2012, Inoue et al., 2013, Yamagata et al., 2013). Thus, these studies
collectively show that tooth-derived stem cells are a highly proliferative, multi-potent, and
self-renewing ecto-mesenchymal stem cell-like population that actively secretes a broad
repertoire of trophic and immunomodulatory factors.
3. Brief overview of the pathophysiology of SCI
The development of effective treatments for SCI has been stifled by this injury's complicated
pathophysiology. During the acute phase, a primary mechanical insult disrupts tissue
homeostasis. This triggers a secondary response, in which activated resident microglia and
infiltrating blood-derived macrophages initiate severe inflammation by releasing high levels
of multiple neurotoxic factors that induce the necrotic and apoptotic death of neurons,
astrocytes, and oligodendrocytes. This response spreads beyond the initial injury site, and
leads to irreversible axonal damage and demyelination (Schwab et al., 2006, Popovich and
Longbrake, 2008, Rowland et al., 2008). Subsequently, reactive astrocytes and oligodendro‐
cytes near the site of the injured spinal cord (SC) respectively produce chondroitin sulfate
proteoglycans (CSPG) and myelin proteins (including myelin-associated glycoprotein (MAG),
Nogo, OMG, Netrin, Semaphorin, and Ephrin). These extracellular molecules function as axon
growth inhibitors (AGIs), acting through the intracellular Rho GTPase signaling cascade
(Silver and Miller, 2004, Yiu and He, 2006). Thus, multiple pathogenic signals act to synergis‐
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