Neurodegenerative interrelated pathophysiological metabolic cascades that are far

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Last updated: August 29, 2019

Neurodegenerativedisorders are heterogeneous and complex, and involve interrelatedpathophysiological metabolic cascades that are far from an ideal clinicalcondition.

However, for functional recovery,the stem cell therapy for neurodegenerative diseases requires a cellularapproach that has the potential to induce all the neurorestorative processes. Differenttypes of stem cells are available for neurodegenerative therapy and DSCs areamongst one of them. The advantages associated with these cells are summarizedbelow:Thedental stem cells (DSCs) are post-natal stem cell populations that have MSC-likecharacteristics, including the capacity for self-renewal and multilineagedifferentiation potential, which make them oneof the promising candidates for cell therapy in neurodegenerative disorders. Noninvasiveisolation, ease of harvesting, readily accessibility and strong therapeuticability again makes them an attractivecandidate. These cells have no ethical issues which is often associated withother cell types (Yalvac et al., 2009) e.g. iPSCs, and have highimmunosuppressive activity (Kerkis et al.

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, 2008 and Pierdomenico et al., 2005).Since these cells are derived from the neural crest, they have a differentorigin from bone-marrow-derived mesenchymal stem cells (BMMSCs), which arederived from mesoderm (Komada et al.

, 2012). In the presence of specificstimuli, these DPSCs differentiated into several brain cell types, includingneurons, glia etc. depicting their neurogenic potential. Interestingly, thesecells show clonogenicity, and high ex vivo proliferative capacity (Akiyamaet al., 2012; Shi et al., 2005) compare to mesenchymal stem cells (MSCs), and areless prone to malignancy (Wilson et al.

, 2015), thus can generate sufficientcells for cell therapy. DSCs have exhibited higher neurogenesis (Isobe et al.,2016), and are capable of influencing endogenous recruitment of stem cells andgenerates neurospheres (Marten et al., 2013). DSCs are also found to be moredeveloped and metabolically active than bone marrow derived MSCs (Karaoz etal.

, 2011). DSCs when compared to umbilical cord stem cells showed lesscellular senescence (Ren et al., 2016), which can be correlated to theincreased expression of genes related to growth factors (Kang et al., 2016). Beneficialeffects on angiogenesis, neurotrophical secretion, and immunomodulation havebeen well defined for them. Importantly they show target migration towards(Leong et al.

, 2012) the lesion site, which is the target for therapeuticintervention.  Further, due to improveddental hygiene autologous transplantation for these cells are readily available. There is a stronganticipation that in the coming decade, stem cell and tissue engineeringtherapies will advance. Dental derived stem cells hold immense medicalpromises, and have drawn attention in recent years because of theiraccessibility, plasticity, and high proliferative ability.  The DSCscan undergo self-renewal and have multipotent differentiation ability, but donot have the ethical issues associated with other sources of stem cells.Although DSCs therapy is a fascinating new approach for the repair of defectiveneural tissues, however, some parameters such as stem cell density andavailability have to be optimized through clinical research (Herberts et al.,2011). DSCs banking by cryopreserving, may provide a potential solutionthough not only time-consuming and costly but also limits their use in clinicalapplications.

 Clinical trials which are double-blind randomized have to beperformed to confirm the true regenerative power of these stem cells. The riskof transmission of bacterial, viral, and fungal or prion pathogens, is a majorcomplication, which may lead to lethal consequences. To conclude, DSCs therapyhas a promising future in neural tissue regeneration and the management ofdisease. However, because stem cell technology is still in its infancy,interdisciplinary cooperation is needed to achieve successful neurologicalapplications. The tissue engineering methodologies combined with a therapeuticpotential of dental stem cells will provide powerful tools for a broaderapplication of dental stem cells in various neurological therapeuticstrategies. Schematic illustration of the dental tissue from which different populationsof DSCs can be isolated.

Subpopulations can be categorized according to theirtissue of origin: dental pulp stem cells, human exfoliated deciduous teeth(SHED), stem cells from the apical papilla (SCAP), tooth germ progenitor cells,gingival mesenchymal stem cells (GFSCs), dental follicle stem cell (DFSCs),alveolar bone-derived mesenchymal stem cells (ABMSCs) and periodontal ligamentstem cells (PDLSCs).  Differentiationpotential of dental pulp stem cells into various cell types is illustratedabove of the figure. Scheme ofmechanistic processes involved in DSCs induced neuroprotection inneurodegenerative diseases.

Transplanted DSCs activate an array of restorativeevents possibly by cell replacement or through parenchymal cell secretion ofgrowth and trophic factors. These factors remodel brain or spinal cord bybystander effects. 

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