Oxysterols in adipose tissue-derived mesenchymal stem cell proliferation and death

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 169; pp. 164 - 175
• Main Authors: Silva, Suelen Feitoza, Levy, Débora, Ruiz, Jorge Luis Maria, de Melo, Thatiana Correa, Isaac, Cesar, Fidelis, Maíra Luísa, Rodrigues, Alessandro, Bydlowski, Sérgio Paulo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2017; Elsevier BV
• Subjects: Acetic acid; Actins - metabolism; Adipose tissue; Adipose Tissue - cytology; Adult; Apoptosis; Autophagy; Caspase 3 - metabolism; Caspase 7 - metabolism; Cell Cycle; Cell death; Cell lines; Cell Proliferation; Cell self-renewal; Cell Survival; Cholestanes - pharmacology; Cholesterol; Cytotoxicity; Female; Fluorescent Antibody Technique, Indirect; Humans; Ketocholesterols - pharmacology; Membrane Potentials; Mesenchymal stem cell; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchyme; Middle Aged; Mitochondria - metabolism; Mitochondrial hyperpolarization; Necrosis; Oxidation; Oxidation-Reduction; Oxysterol; Oxysterols - pharmacology; Phagocytosis; Stem cells; Studies; Mesenchymal stem cell; Mitochondrial hyperpolarization; Adipose tissue; Cell death; Oxysterol; Apoptosis
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2016.04.017

•Mesenchymal stem cells (MSCs) were derived from human adipose tissue.•Short-term effects of oxysterols in MSCs death and proliferation were examined.•Effects were dependent on the type of oxysterol and its concentration.•Active oxysterols led to MSCs death and inhibited their proliferation.•Cell death was complex and included apoptosis, necrosis and autophagy. Mesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Oxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and non-enzymatic oxidation. Potent effects in cell death processes, including cytoxicity and apoptosis induction, were described in several cell lines. Very little is known about the effects of oxysterols in MSCs. 7-ketocholesterol (7-KC), one of the most important oxysterols, was shown to be cytotoxic to human adipose tissue-derived MSCs. Here, we describe the short-term (24h) cytotoxic effects of cholestan-3α-5β-6α-triol, 3,5 cholestan-7-one, (3α-5β-6α)- cholestane-3,6-diol, 7-oxocholest-5-en-3β-yl acetate, and 5β-6β epoxy-cholesterol, on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from three young, healthy women. Oxysterols, with the exception of 3,5 cholestan-7-one and 7-oxocholest-5-en-3β-yl acetate, led to a complex mode of cell death that include apoptosis, necrosis and autophagy, depending on the type of oxysterol and concentration, being cholestan-3α-5β-6α-triol the most effective. Inhibition of proliferation was also promoted by these oxysterols, but no changes in cell cycle were observed.