Low ATP level is sufficient to maintain the uncommitted state of multipotent mesenchymal stem cells

Буравкова, Л. Б.; Rylova, Yu. V.; Andreeva, E. R.; Куликов, А. В.; Pogodina, M. V.; Zhivotovsky, Boris; Gogvadze, Vladimir

doi:10.1016/j.bbagen.2013.05.029

Cited by 46 publications

(53 citation statements)

References 38 publications

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“…The serious alterations in cellular metabolism had underlined the above-described changes in ASC functions. We have shown that the permanent expansion of ASCs at 5% O 2 lowered the cellular ATP level in these cells, diminishing mitochondrial ATP production and stimulating glycolytic ATP production compared to ASCs at standard 20% O 2 [Buravkova et al, 2013]. These data have been confirmed by others [Yamamoto et al, 2013;Choi et al, 2014;Fotia et al, 2014].…”

Section: Introductionsupporting

confidence: 80%

“…It has been clearly demonstrated that MSCs permanently expanded under tissue-related O 2 values (1-10%) display a significant alteration in their properties regardless of the tissue source [Buravkova et al, 2014;Madrigal et al, 2014]. Previously, we have demonstrated that stromal precursors from the stromal-vascular fraction of adipose tissue (adipose stromal cells, ASCs) under 5% O 2 displayed unchanged phenotype and viability, increased proliferative activity and attenuated osteogenic/adipogenic lineage commitment [Buravkova et al, 2009[Buravkova et al, , 2013. The serious alterations in cellular metabolism had underlined the above-described changes in ASC functions.…”

Section: Introductionmentioning

confidence: 99%

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Response of Adipose Tissue-Derived Stromal Cells in Tissue-Related O<sub>2</sub> Microenvironment to Short-Term Hypoxic Stress

Andreeva

Lobanova

Udartseva

et al. 2014

Cells Tissues Organs

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A microenvironment low in O₂ (‘physiological' hypoxia) governs the functions of perivascular multipotent mesenchymal stromal cells, defining their involvement in tissue physiological homeostasis and regenerative remodelling. Acute hypoxic stress is considered as one of the important factors inducing tissue damage. Here, we evaluate the influence of short-term hypoxia (1% O₂ for 24 h) on perivascular adipose tissue-derived cells (ASCs) permanently expanded in tissue-related O₂ (5%) microenvironment. After hypoxic exposure, ASCs retained high viability, stromal cell morphology and mesenchymal phenotype (CD73+, CD90+, CD105+ and CD45-). Mild oxidative damage was unveiled as elevation of reactive oxygen species and thiobarbituric acid-active products, while no reduction in the activity of the antioxidant enzymes catalase and glutathione peroxidase and a 20% statistically significant increase in superoxide dismutase activity was detected. Expression of hypoxia-inducible factor (HIF)-1α and HIF-3α isoforms was differently regulated. HIF-1α displayed transient up-regulation, with maximum levels 30 min after acute hypoxic exposure, while HIF-3α was significantly up-regulated after 24 h. Up-regulation of ERK7, MEK1 and c-fos, and down-regulation of MKK6, p53, CCNA2, CCNB1 and CCNB2 were observed after 24 h of oxygen deprivation. Acute hypoxic exposure did not affect the gene expression of other mitogen-activated protein kinases (MAPKs) and MAPK kinases, MAPK/ERK kinase-interacting proteins, MAPK-activated transcription factors and scaffolding proteins. Significant stimulation of vascular endothelial growth factor α and interleukin-6 production was detected in ASC-conditioned medium. Thus, tissue O₂-adapted ASCs are resistant to hypoxic stress, which can ensure their effective involvement in the regeneration of tissue damage under significant oxygen deprivation.

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Section: Introductionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Response of Adipose Tissue-Derived Stromal Cells in Tissue-Related O<sub>2</sub> Microenvironment to Short-Term Hypoxic Stress

Andreeva

Lobanova

Udartseva

et al. 2014

Cells Tissues Organs

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“…Indeed, adipose tissue-derived MSCs have been reported to survive using low ATP levels in presence of severe hypoxia [41]. This is an important biological advantage for MSCs that can be functional in challenging unexpected periods of stress and this in turn would prolong their life in the uncommitted state.…”

Section: Discussionmentioning

confidence: 99%

Influence of Egr-1 in Cardiac Tissue-Derived Mesenchymal Stem Cells in Response to Glucose Variations

Bastianelli¹,

Siciliano

Puca³

et al. 2014

BioMed Research International

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Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our aim was to investigate how short-term changes in in vitro glucose concentrations affect multipotent cardiac tissue-derived MSCs (cMSCs) in a mouse model of Egr-1 KO (Egr-1−/−). Results showed that loss of Egr-1 does not significantly influence cMSC proliferation. In contrast, responses to glucose variations were observed in wt but not in Egr-1−/− cMSCs by clonogenic assay. Phenotype analysis by RT-PCR showed that cMSCs Egr-1−/− lost the ability to regulate the glucose transporters GLUT-1 and GLUT-4 and, as expected, the Egr-1 target genes VEGF, TGFβ-1, and p300. Acetylated protein levels of H3 histone were impaired in Egr-1−/− compared to wt cMSCs. We propose that Egr-1 acts as immediate glucose biological sensor in cMSCs after a short period of stimuli, likely inducing epigenetic modifications.

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“…При этом стоит отметить, что в зоне повреждения существенно меняется микроокружение, в том числе содержание кислорода. Экспериментальные исследования свидетельствуют об изменении функциональных свойств ММСК в условиях гипоксии [15,16].…”

Section: обоснованиеunclassified

The effects of cysplatin on human adipose tissue derived mesenchymal stromal cells under different oxygen levels

2016

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Low ATP level is sufficient to maintain the uncommitted state of multipotent mesenchymal stem cells

Cited by 46 publications

References 38 publications

Response of Adipose Tissue-Derived Stromal Cells in Tissue-Related O<sub>2</sub> Microenvironment to Short-Term Hypoxic Stress

Response of Adipose Tissue-Derived Stromal Cells in Tissue-Related O<sub>2</sub> Microenvironment to Short-Term Hypoxic Stress

Influence of Egr-1 in Cardiac Tissue-Derived Mesenchymal Stem Cells in Response to Glucose Variations

The effects of cysplatin on human adipose tissue derived mesenchymal stromal cells under different oxygen levels

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