Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome

0510527 - BTÚ 2020 RIV CH eng J - Journal Article
Smieszek, A. - Kornicka, K. - Szlapka-Kosarzewska, J. - Androvič, Peter - Valihrach, Lukáš - Langerová, Lucie - Rohlová, Eva - Kubista, Mikael - Marycz, K.
Metformin Increases Proliferative Activity and Viability of Multipotent Stromal Stem Cells Isolated from Adipose Tissue Derived from Horses with Equine Metabolic Syndrome.
Cells. Roč. 8, č. 2 (2019), č. článku 80. E-ISSN 2073-4409
R&D Projects: GA ČR(CZ) GA18-21942S; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:86652036
Keywords : adipose-derived stromal cells * equine metabolic syndrome * metformin
OECD category: Cell biology
Impact factor: 4.366, year: 2019
Method of publishing: Open access
https://www.mdpi.com/2073-4409/8/2/80

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.
Permanent Link: http://hdl.handle.net/11104/0301055