title: Stressed stem cells: Temperature response in aged mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) derived from young (6 week) and aged (56 week) Wistar rats were cultured at standard (37 degrees C) and reduced (32 degrees C) temperature and compared for age markers and stress levels. (ROS, NO, TBARS, carbonyls, lipofuscin, SOD, GPx, apoptosis, proteasome activity) and heat shock proteins (HSP27, -60, -70, -90). Aged MSCs display many of the stress markers associated with aging in other cell types, but results vary across marker categories and are temperature dependant. In young MSCs, culturing at reduced temperature had a generally beneficial effect: the anti-apoptotic heat shock proteins HSP 27, HSP70, and HSP90 were up-regulated; pro-apoptotic HSP60 was downregulated; SOD, GPx increased; and levels in ROS, NO, TBARS, carbonyl, and lipofuscin were diminished. Apoptosis was reduced, but also proteasome activity. In contrast, in aged MSCs, culturing at reduced temperature generally produced no 'beneficial' changes in these parameters, and can even have detrimental effects. Implications for tissue engineering and for stem cell gerontology are discussed. The results suggest that a 'hormesis' theory of stress response can be extended to MSCs, but that cooling cultivation temperature stress produces positive effects in young cells only.
authors.affiliation: Department of Engineering Material, Centre for Tissue Engineering and Biomaterials, University of Sheffield, Sheffield, UK. A.Stolzing@sheffield.ac.uk
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stolzing
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sethe
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scutt
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis; D016922:Cellular Senescence; D005260:Female; D005434:Flow Cytometry; D005979:Glutathione Peroxidase / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D008062:Lipofuscin / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000473:pathology* / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013696:Temperature; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D008062:Lipofuscin; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase