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https://www.arca.fiocruz.br/handle/icict/20518
SIMVASTATIN MODULATES MESENCHYMAL STROMAL CELL PROLIFERATION AND GENE EXPRESSION
Células estromais mesenquimais
Genetica
Proliferação celular
Leucócitos mononucleares
Células cultivadas
Humanos
Mesenchymal Stromal Cells
Gene Expression
Cell Proliferation
Leukocytes, Mononuclear
Cells, Cultured
Humans
Author
Affilliation
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Center for Cell-Based. Therapy Regional Blood Center of Ribeirão Preto. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
Abstract
Statins 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.
Keywords in Portuguese
SimvastatinaCélulas estromais mesenquimais
Genetica
Proliferação celular
Leucócitos mononucleares
Células cultivadas
Humanos
Keywords
SimvastatinMesenchymal Stromal Cells
Gene Expression
Cell Proliferation
Leukocytes, Mononuclear
Cells, Cultured
Humans
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