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Cells 2018, 7(12), 250; https://doi.org/10.3390/cells7120250

Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro

1
Department of Internal Medicine, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
2
Center for Stem Cell Research, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
3
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
4
Department of Microbiology and Clinical Parasitology, College of Medicine King Khalid University, Abha 61421, Saudi Arabia
5
Department of Biochemistry, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
6
Department of Chemistry, Division of Biochemistry, Faculty of Science, Tanta University, Tanta City 31512, Egypt
*
Author to whom correspondence should be addressed.
Received: 24 October 2018 / Accepted: 4 December 2018 / Published: 6 December 2018
(This article belongs to the Section Stem Cells)
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Abstract

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-β, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-κB and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-β, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-κB and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro. View Full-Text
Keywords: cerebral ischemia; neuroinflammation; MSCs coculture; MSC rescue; in vitro neuronal differentiation cerebral ischemia; neuroinflammation; MSCs coculture; MSC rescue; in vitro neuronal differentiation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Alhazzani, A.; Rajagopalan, P.; Albarqi, Z.; Devaraj, A.; Mohamed, M.H.; Al-Hakami, A.; Chandramoorthy, H.C. Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro. Cells 2018, 7, 250.

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