Low-dose pesticide mixture induces accelerated mesenchymal stem cells aging in vitro

International audienceThe general population is chronically exposed to multiple environmental contaminants such as pesticides. We have previously demonstrated that human mesenchymal stem cells (MSC) exposed in vitro to low doses of a mixture of seven common pesticides showed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation toward adipogenesis. We thus hypothesized that common combination of pesticides may induce a premature cellular aging of adult MSC. Our goal was to evaluate if the prolonged exposure to pesticide mixture could accelerate aging-related markers and in particular deteriorate the immunosuppressive properties of MSCs. MSC exposed to pesticide mixture, under long-term culture and obtained from aging donor were compared by bulk RNA sequencing analysis. Aging, senescence and immunomodulatory markers were compared. The protein expression of cellular aging-associated metabolic markers and of immune function of MSC were analyzed. Functional analysis of the secretome impact on immu-nomodulatory properties of MSC was realized after 21-days exposure to pesticide mixture. The RNA sequencing analysis of MSC exposed to pesticide showed some similarities with cells from prolonged culture, but also with the MSCs of an aged donor. Metabolic markers MDH1, GOT, SIRT3, associated with cellular aging were modified, and altered active T cells regulation, cyto-kines production modifications (IL-10, IL-6, CCL2, TGFβ), usually associated with cellular aging, were also observed. A functional profile modified were found with similarities with aging process. STEM CELLS ;9999:00-0

Low-dose pesticide mixture induces accelerated mesenchymal stem cells aging in vitro

International audienceThe general population is chronically exposed to multiple environmental contaminants such as pesticides. We have previously demonstrated that human mesenchymal stem cells (MSC) exposed in vitro to low doses of a mixture of seven common pesticides showed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation toward adipogenesis. We thus hypothesized that common combination of pesticides may induce a premature cellular aging of adult MSC. Our goal was to evaluate if the prolonged exposure to pesticide mixture could accelerate aging-related markers and in particular deteriorate the immunosuppressive properties of MSCs. MSC exposed to pesticide mixture, under long-term culture and obtained from aging donor were compared by bulk RNA sequencing analysis. Aging, senescence and immunomodulatory markers were compared. The protein expression of cellular aging-associated metabolic markers and of immune function of MSC were analyzed. Functional analysis of the secretome impact on immu-nomodulatory properties of MSC was realized after 21-days exposure to pesticide mixture. The RNA sequencing analysis of MSC exposed to pesticide showed some similarities with cells from prolonged culture, but also with the MSCs of an aged donor. Metabolic markers MDH1, GOT, SIRT3, associated with cellular aging were modified, and altered active T cells regulation, cyto-kines production modifications (IL-10, IL-6, CCL2, TGFβ), usually associated with cellular aging, were also observed. A functional profile modified were found with similarities with aging process. STEM CELLS ;9999:00-0