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Mechanisms underlying dental-derived stem cell-mediated neurorestoration in neurodegenerative disorders.

ABSTRACT: BACKGROUND:Neurodegenerative disorders have a complex pathology and are characterized by a progressive loss of neuronal architecture in the brain or spinal cord. Neuroprotective agents have demonstrated promising results at the preclinical stage, but this has not been confirmed at the clinical stage. Thus far, no neuroprotective drug that can prevent neuronal degeneration in patients with neurodegenerative disorders is available. MAIN BODY:Recent studies have focused on neurorestorative measures, such as cell-based therapy, rather than neuroprotective treatment. The utility of cell-based approaches for the treatment of neurodegenerative disorders has been explored extensively, and the results have been somewhat promising with regard to reversing the outcome. Because of their neural crest origin, ease of harvest, accessibility, ethical suitability, and potential to differentiate into the neurogenic lineage, dental-derived stem cells (DSCs) have become an attractive source for cell-based neurorestoration therapies. In the present review, we summarize the possible use of DSC-based neurorestoration therapy as an alternative treatment for neurodegenerative disorders, with a particular emphasis on the mechanism underlying recovery in neurodegenerative disorders. CONCLUSION:Transplantation research in neurodegenerative diseases should aim to understand the mechanism providing benefits both at the molecular and functional level. Due to their ease of accessibility, plasticity, and ethical suitability, DSCs hold promise to overcome the existing challenges in the field of neurodegeneration through multiple mechanisms, such as cell replacement, bystander effect, vasculogenesis, synaptogenesis, immunomodulation, and by inhibiting apoptosis.

SUBMITTER: Raza SS

PROVIDER: S-EPMC6158826 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Mechanisms underlying dental-derived stem cell-mediated neurorestoration in neurodegenerative disorders.

Raza Syed Shadab SS Wagner Aurel Popa AP Hussain Yawer S YS Khan Mohsin Ali MA

Stem cell research & therapy 20180926 1

<h4>Background</h4>Neurodegenerative disorders have a complex pathology and are characterized by a progressive loss of neuronal architecture in the brain or spinal cord. Neuroprotective agents have demonstrated promising results at the preclinical stage, but this has not been confirmed at the clinical stage. Thus far, no neuroprotective drug that can prevent neuronal degeneration in patients with neurodegenerative disorders is available.<h4>Main body</h4>Recent studies have focused on neuroresto ...[more]

PMID: 30257724

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Project description:BackgroundStem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34(+), and CD133(+) cells, with that in unsorted, nucleated cells (NCs).Methods and resultsThe expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+), and CD133(+) cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+), and CD133(+) cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+) or CD133(+) cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation.ConclusionsCollectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

Dataset Information

Mechanisms underlying dental-derived stem cell-mediated neurorestoration in neurodegenerative disorders.

Publications

Mechanisms underlying dental-derived stem cell-mediated neurorestoration in neurodegenerative disorders.

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