Endocrine Abstracts (2006) 11 P44

Selenium supplementation restores the antioxidative capacity and prevents cell damage in mesenchymal stem cells in vitro

R Ebert1, M Ulmer1, S Zeck1, J Meissner-Weigl1, D Schneider1, H Stopper1, N Schupp1, M Kassem2 & F Jakob1

1University of Wuerzburg, Wuerzburg, Germany; 2University Hospital, Odense, Denmark.

Mesenchymal stem cells (MSC) are developed for cell based therapeutic strategies and undergo cellular stress during ex vivo procedures. Reactive oxygen species (ROS) of environmental and cellular origin are involved in redox signaling, cumulative cell damage, senescence and tumor development. Selenium independent (superoxide dismutases 1 and 2 (SOD1 and SOD2) and catalase (CAT)) and selenium dependent (glutathione peroxidases (GPx), thioredoxin reductases (TrxR)) enzymes regulate cellular ROS steady state levels. SOD process superoxide anion to hydrogen peroxide, which is subsequently neutralized by CAT and GPx.

Human primary MSC and telomerase-immortalized human mesenchymal stem cells (hMSC-TERT) express SOD1 and 2, CAT, GPx 1-3 and TrxR1 and 2. We show here that the activity of antioxidative selenium dependent enzymes is impaired in primary MSC and hMSC-TERT in standard cell cultures (5–10% FCS, selenite 5–10 nM). Under these conditions the superoxide anion processing enzyme SOD1 is not sufficiently stimulated by a ROS load. Resulting oxidative burden favors generation of micronuclei in MSC, which is a readout for DNA damage. Supplementing the cell culture medium with selenite (100 nM) restores basal GPx and TrxR activity, rescues basal and ROS-stimulated SOD1 mRNA expression and activity, and reduces ROS accumulation in hMSC-TERT and micronuclei formation in primary MSC.

In conclusion mesenchymal stem cells in routine cell culture have low antioxidative capacity and are subjected to oxidative stress as indicated by the generation of micronuclei. Selenite supplementation of MSC 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.

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