Selenium supplementation restores the antioxidative capacity and prevents cell damage in bone marrow stromal cells in vitro

¹ Musculosceletal Research Center, Orthopaedic Department, University of Wüerzburg, Brettreichstrasse, Wüerzburg, Germany
² Institute of Pharmacology and Toxicology, University of Wüerzburg, Versbacher Strasse, Wüerzburg, Germany
³ Department of Endocrinology, University Hospital of Odense, DK-5000 Odense C, Denmark

^* To whom correspondence should be addressed. E-mail: f-jakob.klh{at}mail.uni-wuerzburg.de.

	Abstract

Bone marrow stromal cells (BMSC) and other cell populations derived from mesenchymal precursors are developed for cell based therapeutic strategies and undergo cellular stress during ex vivo procedures. Reactive oxygen species (ROS) of cellular and environmental origin are involved in redox signaling, cumulative cell damage, senescence and tumor development. Selenium dependent (glutathione peroxidases (GPx), thioredoxin reductases (TrxR)) and independent (superoxide dismutases (SOD) and catalase (CAT)) enzyme systems regulate cellular ROS steady state levels. SOD process superoxide anion to hydrogen peroxide, which is subsequently neutralized by GPx and CAT, TrxR neutralizes other ROS like peroxinitrite. Primary BMSC and telomerase-immortalized human mesenchymal stem cells (hMSC-TERT) express GPx 1-3, TrxR1 and 2, SOD1 and 2 and CAT. We show here that in standard cell cultures (5-10% FCS, selenite 5-10 nM) the activity of antioxidative selenoenzymes is impaired in hMSC-TERT and BMSC. Under these conditions the superoxide anion processing enzyme SOD1 is not sufficiently stimulated by an ROS load. Resulting oxidative stress favors generation of micronuclei in BMSC. Supplementation of selenite (100 nM) restores basal GPx and TrxR activity, rescues basal and ROS-stimulated SOD1 mRNA expression and activity, reduces ROS accumulation in hMSC-TERT and micronuclei generation in BMSC. In conclusion BMSC in routine cell culture have low antioxidative capacity and are subjected to oxidative stress as indicated by the generation of micronuclei. Selenite supplementation of BMSC cell cultures appears to be an important countermeasure to restore their antioxidative capacity and to reduce cell damage in the context of tissue engineering and transplantation procedures.