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.

译文

来自年轻 (6周) 和老年 (56周) Wistar大鼠的间充质干细胞 (msc) 在标准 (37 ℃) 和降低 (32 ℃) 温度下培养,并比较年龄标记物和应激水平。(ROS,NO,TBARS,羰基,脂褐素,SOD,GPx,凋亡,蛋白酶体活性) 和热休克蛋白 (HSP27,-60,-70,-90)。老化的msc在其他细胞类型中显示出许多与衰老相关的应激标记,但结果因标记类别而异,并且与温度有关。在年轻的msc中,在低温下培养通常具有有益的作用: 抗凋亡热休克蛋白HSP 27,HSP70和HSP90上调; 促凋亡HSP60下调; SOD,GPx增加; ROS,NO,TBARS,羰基,脂褐素减少了。细胞凋亡降低,但蛋白酶体活性也降低。相反,在老化的msc中,在降低的温度下进行培养通常不会对这些参数产生 “有益的” 变化,甚至可能产生不利影响。讨论了对组织工程和干细胞老年学的影响。结果表明,应激反应的 “hormesis” 理论可以扩展到msc,但是冷却的培养温度胁迫仅在年轻细胞中产生积极影响。

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