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首页> 外文期刊>Journal of Cellular Physiology >Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired
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Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired

机译：骨髓间充质干细胞捐赠者的高身体质量指数显示内质的升高网压力和功能受损

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摘要

Bone marrow mesenchymal stem cells (BM-MSCs) are promising candidates for regenerative medicine purposes. The effect of obesity on the function of BM-MSCs is currently unknown. Here, we assessed how obesity affects the function of BM-MSCs and the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) therein. BM-MSCs were obtained from healthy donors with a normal (25) or high (30) body mass index (BMI). High-BMI BM-MSCs displayed severely impaired osteogenic and diminished adipogenic differentiation, decreased proliferation rates, increased senescence, and elevated expression of ER stress-related genes ATF4 and CHOP. Suppression of ER stress using tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (4-PBA) resulted in partial recovery of osteogenic differentiation capacity, with a significant increase in the expression of ALPL and improvement in the UPR. These data indicate that BMI is important during the selection of BM-MSC donors for regenerative medicine purposes and that application of high-BMI BM-MSCs with TUDCA or 4-PBA may improve stem cell function. However, whether this improvement can be translated into an in vivo clinical advantage remains to be assessed.
机译：骨髓间充质干细胞(BM-MSCs)有前途的候选人为再生医学目的。BM-MSCs目前未知。评估肥胖如何影响的功能BM-MSCs和内质网的作用(ER)压力和展开的蛋白质反应(UPR)。捐助者与正常(& 25)或高(在30)身体质量指数(BMI)。严重受损的成骨和减弱脂肪形成的分化,减少扩散率,增加了衰老,ER应激相关基因的表达升高ATF4和排骨。tauroursodeoxycholic酸(TUDCA)和4-phenylbutyrate (4-PBA)导致部分复苏的成骨分化能力,的表达显著增加UPR ALPL和改进。表明,BMI在是很重要的选择BM-MSC捐助者的再生医学目的的应用高bmi指数BM-MSCs TUDCA或4-PBA可能会改善干细胞的功能。改善体内可以转化为一个临床优势还有待评估。

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