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

• DOI: 10.1016/j.jsbmb.2016.04.017
• Publication Date: 2016-04-30T17:38:59Z
• Authors: Suelen Feitoza Silva; Débora Levy; Jorge Luis Maria ...; Thatiana Correa d...; Cesar Isaac; Maíra Luísa Fidelis; Alessandro Rodrigues; Sérgio Paulo Bydl...
• Keywords: Cell death; Adult; Cell Survival; Adipose tissue; Apoptosis; Mitochondrial hyperpolarization; Membrane Potentials; Necrosis; 03 medical and health sciences; Oxysterol; Autophagy; Humans; Fluorescent Antibody Technique, Indirect; Ketocholesterols; Mesenchymal stem cell; Cell Proliferation; Caspase 7; 0303 health sciences; Cholestanes; Caspase 3; Cell Cycle; Mesenchymal Stem Cells; Middle Aged; Actins; Mitochondria; 3. Good health; Adipose Tissue; Female

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.