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Human Wharton's jelly mesenchymal stem cells protect neural cells from oxidative stress through paracrine mechanisms.

ABSTRACT: Aim:Mesenchymal stem cells (MSCs) have neuroprotective and immunomodulatory properties, which are partly mediated by extracellular vesicles (EVs) secretion. We aimed to evaluate the effects of human Wharton's jelly-derived MSCs (WJ-MSCs) and their EVs on rat hippocampal cultures subjected to hydrogen peroxide (H2O2). Materials & methods:Hippocampal dissociated cultures were either co-cultured with WJ-MSCs or treated with their EVs prior to H2O2 exposure and reactive oxygen species levels and cell viability were evaluated. Results:Coculture with WJ-MSCs or pre-incubation with EVs prior to the insult reduced reactive oxygen species after H2O2 exposure. Cell viability was improved only when coculture was maintained following the insult, while EVs did not significantly improve cell viability. Conclusion:WJ-MSCs have potential antioxidant and neuroprotective effects on hippocampal cultures which might be partially mediated by EVs.

SUBMITTER: Puig-Pijuan T

PROVIDER: S-EPMC7668126 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Human Wharton's jelly mesenchymal stem cells protect neural cells from oxidative stress through paracrine mechanisms.

Puig-Pijuan Teresa T de Godoy Mariana A MA Pinheiro Carvalho Luiza Rachel LR Bodart-Santos Victor V Lindoso Rafael Soares RS Pimentel-Coelho Pedro Moreno PM Mendez-Otero Rosalia R

Future science OA 20200917 9

<h4>Aim</h4>Mesenchymal stem cells (MSCs) have neuroprotective and immunomodulatory properties, which are partly mediated by extracellular vesicles (EVs) secretion. We aimed to evaluate the effects of human Wharton's jelly-derived MSCs (WJ-MSCs) and their EVs on rat hippocampal cultures subjected to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>).<h4>Materials & methods</h4>Hippocampal dissociated cultures were either co-cultured with WJ-MSCs or treated with their EVs prior to H<sub>2</sub>O<sub> ...[more]

PMID: 33235812

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Project description:Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are a novel and promising strategy for tissue engineering because of their ability to differentiate into many cell types. We characterized the differentiation of WJ-MSCs into endometrial epithelial cell (EEC)-like and endometrial stromal cell (ESC)-like cells and assessed the effect of 17?-estradiol and 8-Br-cAMP on the differentiation system.WJ-MSCs were treated in two ways to differentiate into EEC-like and ESC-like cells respectively: cocultured with ESCs in control/differentiation medium (17?-estradiol, growth factors); and cultured in control/differentiation medium (8-Br-cAMP alone or 8-Br-cAMP plus 17?-estrogen and growth factors). Three signaling pathway inhibitors (SB203580, PD98059, H89) were used to investigate the mechanism of WJ-MSC differentiation into ESC-like cells. Immunofluorescence, western blot and flow cytometry analyses were used to analyze expression of epithelial markers and stromal cell markers. Enzyme-linked immunosorbent assays were used to test the production of secretory proteins associated with the differentiation of ESC-like cells.17?-estradiol at 1 ?M downregulated vimentin and CD13 and upregulated cytokeratin and CD9 proteins, promoting the differentiation of WJ-MSCs into EEC-like cells in the coculture system. 8-Br-cAMP at 0.5 mM upregulated vimentin and CD13 and downregulated CK and CD9, promoting the differentiation of WJ-MSCs into ESC-like cells. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) were upregulated and the protein kinase A (PKA) signaling pathway was activated, whereas extracellular signal-regulated (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were not affected.17?-estradiol at 1 ?M is a good inducer for facilitating the differentiation of WJ-MSCs into EEC-like cells. 8-Br-cAMP plus estrogen and growth factors can induce the differentiation of WJ-MSCs into ESC-like cells. During the differentiation of WJ-MSCs into ESC-like cells, PRL and IGFBP1 were upregulated by the treatment and the PKA signaling pathway was activated, whereas ERK1/2 and p38 MAPK were not affected. These findings suggest a promising approach to the treatment of endometrial damage and other endometrial diseases and suggest new applications for WJ-MSCs in clinical practice.

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Human Wharton's jelly mesenchymal stem cells protect neural cells from oxidative stress through paracrine mechanisms.

Publications

Human Wharton's jelly mesenchymal stem cells protect neural cells from oxidative stress through paracrine mechanisms.

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