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Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome
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SYSNO ASEP 0510527 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome Author(s) Smieszek, A. (PL)
Kornicka, K. (PL)
Szlapka-Kosarzewska, J. (PL)
Androvič, Peter (BTO-N)
Valihrach, Lukáš (BTO-N) RID, ORCID
Langerová, Lucie (BTO-N) RID
Rohlová, Eva (BTO-N)
Kubista, Mikael (BTO-N) RID
Marycz, K. (PL)Number of authors 9 Article number 80 Source Title Cells. - : MDPI
Roč. 8, č. 2 (2019)Number of pages 20 s. Language eng - English Country CH - Switzerland Keywords adipose-derived stromal cells ; equine metabolic syndrome ; metformin Subject RIV EB - Genetics ; Molecular Biology OECD category Cell biology R&D Projects GA18-21942S GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BTO-N - RVO:86652036 UT WOS 000460896000002 DOI 10.3390/cells8020080 Annotation In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASC(HE)) and individuals affected by equine metabolic syndrome (EqASC(EMS)). The cells were treated with 0.5 M MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as population doubling time rate (PDT) and distribution of EqASCs in the cell cycle. The influence of metformin on EqASC viability was determined in relation to apoptosis profile, mitochondrial membrane potential, oxidative stress markers and BAX/BCL-2 mRNA ratio. Further, we were interested in possibility of metformin affecting the Wnt3a signalling pathway and, thus, we determined mRNA and protein level of WNT3A andcatenin. Finally, using a two-tailed RT-qPCR method, we investigated the expression of miR-16-5p, miR-21-5p, miR-29a-3p, miR-140-3p and miR-145-5p. Obtained results indicate pro-proliferative and anti-apoptotic effects of metformin on EqASCs. In this study, MF significantly improved proliferation of EqASCs, which manifested in increased synthesis of DNA and lowered PDT value. Additionally, metformin improved metabolism and viability of cells, which correlated with higher mitochondrial membrane potential, reduced apoptosis and increased WNT3A/-catenin expression. Metformin modulates the miRNA expression differently in EqASC(HE) and EqASC(EMS). Metformin may be used as a preconditioning agent which stimulates proliferative activity and viability of EqASCs. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2020 Electronic address https://www.mdpi.com/2073-4409/8/2/80
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