Medical College, Shantou University, Shantou, Guangdong, China.
Department of Emergency Medicine, Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
Oxid Med Cell Longev. 2019 Nov 25;2019:1305049. doi: 10.1155/2019/1305049. eCollection 2019.
Mesenchymal stem cells (MSCs) have shown beneficial effects in the treatment of abdominal aortic aneurysm (AAA). Nonetheless, the biological properties of adipose-derived MSCs (ASCs) from patients with AAA (AAA-ASCs) remain unclear. This study is aimed at investigating the properties of cell phenotype and function of AAA-ASCs compared with ASCs from age-matched healthy donors (H-ASCs). H-ASCs and AAA-ASCs were studied for cell phenotype, differentiation capacity, senescence, and mitochondrial and autophagic functions. Cellular senescence was examined by senescence-associated -galactosidase (SA--gal) staining. Mitochondrial morphology was determined by MitoTracker staining. Despite the similar surface markers of AAA-ASCs and H-ASCs, AAA-ASCs exhibited altered multidifferentiation potential. Compared with H-ASCs, AAA-ASCs displayed enhanced senescence manifested by increased SA--gal activity and decreased proliferation and migration ability. Furthermore, AAA-ASCs showed increased mitochondrial fusion, reactive oxygen species (ROS) production, and decreased mitochondrial membrane potential. In addition, AAA-ASCs exhibited decreased autophagy level, upregulation of IL-6 and TNF- secretion, and downregulation of IL-10 secretion compared with H-ASCs. Nonetheless, treatment of AAA-ASCs with rapamycin (an autophagy activator) dramatically reduced secretion of IL-6 and TNF- and enhanced secretion of IL-10. In conclusion, our study showed that AAA-ASCs exhibit senescence phenomena and decreased cell function. Understanding the specific alterations in AAA-ASCs will help explore novel strategies to restore cell function for AAA treatment.
间充质干细胞 (MSCs) 在治疗腹主动脉瘤 (AAA) 方面显示出有益的效果。然而,AAA 患者来源的脂肪间充质干细胞 (AAA-ASCs) 的生物学特性尚不清楚。本研究旨在研究与年龄匹配的健康供体来源的脂肪间充质干细胞 (H-ASCs) 相比,AAA-ASCs 的细胞表型和功能特性。研究了 H-ASCs 和 AAA-ASCs 的细胞表型、分化能力、衰老、线粒体和自噬功能。通过衰老相关β-半乳糖苷酶 (SA-β-gal) 染色检测细胞衰老。通过 MitoTracker 染色测定线粒体形态。尽管 AAA-ASCs 和 H-ASCs 具有相似的表面标志物,但 AAA-ASCs 表现出改变的多向分化潜能。与 H-ASCs 相比,AAA-ASCs 表现出增强的衰老,表现为 SA-β-gal 活性增加,增殖和迁移能力降低。此外,AAA-ASCs 显示出线粒体融合增加、活性氧 (ROS) 产生增加和线粒体膜电位降低。此外,与 H-ASCs 相比,AAA-ASCs 的自噬水平降低,IL-6 和 TNF- 的分泌上调,IL-10 的分泌下调。然而,用雷帕霉素(自噬激活剂)处理 AAA-ASCs 可显著减少 IL-6 和 TNF-的分泌,并增加 IL-10 的分泌。总之,我们的研究表明,AAA-ASCs 表现出衰老现象和细胞功能降低。了解 AAA-ASCs 的特定变化将有助于探索恢复 AAA 治疗中细胞功能的新策略。