Simvastatin modulates mesenchymal stromal cell proliferation and gene expression

dc.creatorZanette, Dalila Lucíola
dc.creatorLorenzi, Julio Cesar Cetrulo
dc.creatorPanepucci, Rodrigo Alexandre
dc.creatorPalma, Patricia Vianna Bonini
dc.creatorSantos, Daiane Fernanda dos
dc.creatorPrata, Karen Lima
dc.creatorSilva, Wilson Araújo
dc.date2017-08-04T13:58:55Z
dc.date2017-08-04T13:58:55Z
dc.date2015
dc.date.accessioned2023-09-26T22:37:10Z
dc.date.available2023-09-26T22:37:10Z
dc.identifierZANETTE, D. L. et al. Simvastatin modulates mesenchymal stromal cell proliferation and gene expression. PLoS One, v. 10, n. 4, p. e0120137, 2015.
dc.identifier1932-6203
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/20518
dc.identifier10.1371/journal.pone.0120137
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8881093
dc.descriptionZanette, Dalila Lucíola “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.
dc.descriptiongrants 2009/09443-2 and 2013/08135-2, São Paulo Research Foundation (FAPESP) and CNPq
dc.descriptionStatins are widely used hypocholesterolemic drugs that block the mevalonate pathway, responsible for the biosysnthesis of cholesterol. However, statins also have pleiotropic effects that interfere with several signaling pathways. Mesenchymal stromal cells (MSC) are a heterogeneous mixture of cells that can be isolated from a variety of tissues and are identified by the expression of a panel of surface markers and by their ability to differentiate in vitro into osteocytes, adipocytes and chondrocytes. MSC were isolated from amniotic membranes and bone marrows and characterized based on ISCT (International Society for Cell Therapy) minimal criteria. Simvastatin-treated cells and controls were directly assayed by CFSE (Carboxyfluorescein diacetate succinimidyl ester) staining to assess their cell proliferation and their RNA was used for microarray analyses and quantitative PCR (qPCR). These MSC were also evaluated for their ability to inhibit PBMC (peripheral blood mononuclear cells) proliferation. We show here that simvastatin negatively modulates MSC proliferation in a dose-dependent way and regulates the expression of proliferation-related genes. Importantly, we observed that simvastatin increased the percentage of a subset of smaller MSC, which also were actively proliferating. The association of MSC decreased size with increased pluripotency and the accumulating evidence that statins may prevent cellular senescence led us to hypothesize that simvastatin induces a smaller subpopulation that may have increased ability to maintain the entire pool of MSC and also to protect them from cellular senescence induced by long-term cultures/passages in vitro. These results may be important to better understand the pleiotropic effects of statins and its effects on the biology of cells with regenerative potential.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectSimvastatina
dc.subjectCélulas estromais mesenquimais
dc.subjectGenetica
dc.subjectProliferação celular
dc.subjectLeucócitos mononucleares
dc.subjectCélulas cultivadas
dc.subjectHumanos
dc.subjectSimvastatin
dc.subjectMesenchymal Stromal Cells
dc.subjectGene Expression
dc.subjectCell Proliferation
dc.subjectLeukocytes, Mononuclear
dc.subjectCells, Cultured
dc.subjectHumans
dc.titleSimvastatin modulates mesenchymal stromal cell proliferation and gene expression
dc.typeArticle


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