Dataset Information

Neuroprotective properties of Mesenchymal Stromal Cell–Derived Extracellular Vesicles in Models of Acute Brain Pathology

ABSTRACT: Extracellular vesicles (EVs) of multipotent mesenchymal stromal cells (MSCs) in various studies have shown a wide range of cytoprotective effects, including neuroprotective ones. It is important to note that the therapeutic effect of EVs is observed regardless of the tissue from which MSCs were isolated. However, the mechanisms of the neuroprotective action of extracellular vesicles remain elusive. It is assumed that the proteins contained in EVs could make the main contribution to the therapeutic effects of EVs. The aim of this work was to study protein composition of EV obtained from MSCs in conjunction with the experiments on neuroprotective properties and mechanisms of the neuroprotective effects of EVs-MSC in in vitro and in vivo models of acute neurological diseases.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Mesenchymal Stromal Cell, Stem Cell

SUBMITTER: Sergey Kovalchuk

LAB HEAD: Sergey I. Kovalchuk

PROVIDER: PXD027581 | Pride | 2022-10-14

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2020-04-04-td-uniprot-SP_human_can_20191030.fasta	Fasta
	Zorov_microvesicles_001_20191010_KS_ves4-1_4uL-2ug_1_20191012022456.raw	Raw
	Zorov_microvesicles_002_20191010_KS_ves4-1_4uL-2ug_2_20191012034921.raw	Raw
	Zorov_microvesicles_004_20191010_KS_ves4-2_5uL-2ug_1.raw	Raw
	Zorov_microvesicles_005_20191010_KS_ves4-2_5uL-2ug_2.raw	Raw

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Publications

Mesenchymal stromal cell-derived extracellular vesicles afford neuroprotection by modulating PI3K/AKT pathway and calcium oscillations.

Turovsky Egor A EA Golovicheva Victoria V VV Varlamova Elena G EG Danilina Tatyana I TI Goryunov Kirill V KV Shevtsova Yulia A YA Pevzner Irina B IB Zorova Ljubava D LD Babenko Valentina A VA Evtushenko Ekaterina A EA Zharikova Anastasia A AA Khutornenko Anastasia A AA Kovalchuk Sergey I SI Plotnikov Egor Y EY Zorov Dmitry B DB Sukhikh Gennady T GT Silachev Denis N DN

International journal of biological sciences 20220821 14

Mesenchymal stromal cells (MSC) are widely recognized as potential effectors in neuroprotective therapy. The protective properties of MSC were considered to be associated with the secretion of extracellular vesicles (MSC-EV). We explored the effects of MSC-EV <i>in vivo</i> on models of traumatic and hypoxia-ischemia (HI) brain injury. Neuroprotective mechanisms triggered by MSC-EV were also studied <i>in vitro</i> using a primary neuroglial culture. Intranasal administration of MSC-EV reduced t ...[more]

PMID: 36147480

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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.