Obesity Blunts the Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles.
Obesity Blunts the Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles.
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DOI：
10.1016/j.ekir.2023.06.009
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发表时间：
2023-09
影响因子：
6
通讯作者：
Lerman, Lilach O.
中科院分区：
文献类型：
--
作者：
Huang, Weijun;Hong, Siting;Zhu, Xiangyang;Alsaeedi, Mina H.;Tang, Hui;Krier, James D.;Gandhi, Deep;Jordan, Kyra L.;Saadiq, Ishran M.;Jiang, Yamei;Eirin, Alfonso;Lerman, Lilach O.
关键词：
间充质干细胞/基质细胞衍生的细胞外囊泡（MSC-EV）是具有与其亲本细胞相当的治疗功能的旁分泌载体。然而，目前尚不清楚供体肥胖是否影响其治疗功能。我们检验了人脂肪组织来源的MSC-EV（A-MSC-EV）的疗效因肥胖而减弱的假设。MSC-EV通过超离心从间充质干细胞/基质细胞（MSC）分离，所述间充质干细胞/基质细胞（MSC）从肥胖和瘦人受试者（分别为肥胖和瘦-MSC-EV）的腹部皮下脂肪收集，并在肾动脉狭窄（RAS）诱导后2周注射到小鼠的主动脉中。MSC-EV输送后2周进行磁共振成像研究，以确定肾功能。通过组织学和炎症因子（包括白细胞介素（IL）-1β、IL-6、单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子α（TNF-α））的基因表达评估MSC-EV对组织损伤的影响。还评估了氧化损伤、巨噬细胞浸润、血浆肾素和缺氧诱导因子-1 α（HIF-1α）。追踪显示MSC-EV定位于肾脏组织，包括肾小球和肾小管。所有MSC-EV均降低收缩压（SBP）和血浆肾素，并改善狭窄后肾脏（STK）体积，但肥胖MSC-EV在改善髓质缺氧、纤维化和肾小管损伤方面不如瘦MSC-EV有效。Lean-MSC-EV减少了炎症，而肥胖减弱了这种作用。只有lean-MSC-EVs降低STK皮质HIF-1α表达。肥胖减弱了慢性缺血性肾病中人MSC-EV的抗缺氧、抗纤维化、抗炎和肾小管修复功能。这些观察结果可能对肥胖受试者的自我修复能力和再生医学中自体MSC-EV的使用具有影响。
Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) are paracrine vectors with therapeutic functions comparable to their parent cells. However, it remains unclear if donor obesity affects their therapeutic functions. We tested the hypothesis that the curative effect of human adipose tissue-derived MSC-EVs (A-MSC-EVs) is blunted by obesity. MSC-EVs were isolated by ultracentrifugation from mesenchymal stem/stromal cells (MSCs) collected from abdominal subcutaneous fat of obese and lean human subjects (obese and lean-MSC-EVs, respectively) and injected into the aorta of mice 2 weeks after renal artery stenosis (RAS) induction. Magnetic resonance imaging studies were conducted 2 weeks after MSC-EVs delivery to determine renal function. The effect of MSC-EVs on tissue injury was assessed by histology and gene expression of inflammatory factors, including interleukin (IL)-1β, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α). Oxidative damage, macrophage infiltration, plasma renin, and hypoxia inducible factor-1α (HIF-1α) were also assessed. Tracking showed that MSC-EVs localized in the kidney tissue, including glomeruli and tubules. All MSC-EVs decreased systolic blood pressure (SBP) and plasma renin and improved the poststenotic kidney (STK) volume, but obese-MSC-EVs were less effective than lean-MSC-EVs in improving medullary hypoxia, fibrosis, and tubular injury. Lean-MSC-EVs decreased inflammation, whereas obesity attenuated this effect. Only lean-MSC-EVs decreased STK cortical HIF-1α expression. Obesity attenuates the antihypoxia, antifibrosis, antiinflammation, and tubular repair functions of human MSC-EVs in chronic ischemic kidney disease. These observations may have implications for the self-repair potency of obese subjects and for the use of autologous MSC-EVs in regenerative medicine.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
3.7
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