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

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.

17β-Estradiol Modulates SIRT1 and Halts Oxidative Stress-Mediated Cognitive Impairment in a Male Aging Mouse Model

“…According to previous knowledge that 17β-estradiol can bind to its own receptor, ERα [48,49,50,51], we determined whether 17β-estradiol activate SIRT1 through ERα dependent and independent manner. Our Western blot and immunofluorescence results showed that d -gal treatment reduce ERα and SIRT1 expression in adult mouse brain (Figure 4a–c).…”

Cytokine physiognomies of MSCs from varied sources confirm the regenerative commitment post‐coculture with activated neutrophils

“…Neutrophils were isolated by the standard procedure cited elsewhere (Gerasimov & Ignatov, 2004;Lakschevitz & Glogauer, 2014) IN). The purity was determined by the presence of MSCs, which were positive for CD73, CD105, and CD90 expression, and negative for CD34 and CD45 (Alhazzani et al, 2018).…”

Influence of Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Oxidative Stress Intensity in Minimally Conscious State Patients

“…In acute diseases such as stroke, when a large number of neurons are damaged, multiple-fold increases in the amount of CuZn-SOD in the CSF have been found [89,90]. Although MSC therapies are very promising in a number of neurodegenerative disorders [31,[91][92][93], the current results suggest that BM-MSC therapy for MCS patients does not influence SOD activity.…”