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Extracellular Microvesicles (MV's) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells.
Stem Cell Reviews and Reports ( IF 4.8 ) Pub Date : 2020-09-03 , DOI: 10.1007/s12015-020-10035-4
C Weiss 1 , K Kornicka-Grabowska 2, 3 , M Mularczyk 2, 3 , N Siwinska 4 , K Marycz 2, 3, 5
Affiliation  

Extracellular vesicles (EVs), a spherical membrane fragments including exosomes, are released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. As MVs cargo include DNA, RNA, miRNA, lipids and proteins their have gain special attention in the field of regenerative medicine. Depending on the type of transferred molecules, MVs may exert wide range of biological effects in recipient cells including pro-inflammatory and anti-apoptotic action. In presented paper, we isolated MVs form adipose derived mesenchymal stem cells (ASC) which underwent stimulation with 5-azacytydine and resveratrol (AZA/RES) in order to improve their therapeutic potential. Then, isolated MVs were applied to ASC with impaired cytophysiological properties, isolated from equine metabolic syndrome diagnosed animals. Using RT-PCR, immunofluorescence, ELISA, confocal microscopy and western blot, we have evaluated the effects of MVs on recipient cells. We have found, that MVs derived from AZA/RES treated ASC ameliorates apoptosis, senescence and endoplasmic reticulum (ER) stress in deteriorated cells, restoring their proper functions. The work indicates, that cells treated with AZA/RES through their paracrine action can rejuvenate recipient cells. However, further research needs to be performed in order to fully understand the molecular mechanisms of these bioactive factors action.



中文翻译:

从 5-氮杂胞苷和白藜芦醇处理的细胞中分离出的细胞外微泡 (MV) 可提高代谢综合征来源的间充质干细胞的活力并改善内质网应激。

细胞外囊泡(EV)是一种包括外泌体的球形膜片段,由包括间充质基质细胞(MSC)在内的多种细胞类型在组成型或刺激下释放。由于MV的货物包括DNA、RNA、miRNA、脂质和蛋白质,因此它们在再生医学领域受到特别关注。根据转移分子的类型,MV 可能在受体细胞中发挥广泛的生物效应,包括促炎和抗凋亡作用。在本文中,我们从脂肪来源的间充质干细胞 (ASC) 中分离出 MV,这些干细胞接受 5-氮杂胞苷和白藜芦醇 (AZA/RES) 刺激,以提高其治疗潜力。然后,将分离的MV应用于细胞生理学特性受损的ASC,这些ASC是从马代谢综合征诊断的动物中分离出来的。使用 RT-PCR、免疫荧光、ELISA、共聚焦显微镜和蛋白质印迹,我们评估了 MV 对受体细胞的影响。我们发现,源自 AZA/RES 处理的 ASC 的 MV 可改善恶化细胞的凋亡、衰老和内质网 (ER) 应激,恢复其正常功能。这项工作表明,用 AZA/RES 处理的细胞通过其旁分泌作用可以使受体细胞恢复活力。然而,需要进行进一步的研究,以充分了解这些生物活性因子作用的分子机制。

更新日期:2020-09-03
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