Immune-modulatory properties of adipose tissue-derived mesenchymal stem/stromal cells (MSCs) might be susceptible to metabolic disturbances. We hypothesized that the immune-modulatory function of MSCs might be blunted in obese human subjects. MSCs were collected from abdominal subcutaneous fat of obese and lean subjects during bariatric or kidney donation surgeries, respectively. MSCs were co-cultured in vitro for 24 h with M1 macrophages, which were determined as M1or M2 phenotypes by flow cytometry, and cytokines measured in conditioned media. In vivo, lean or obese MSCs (5 × 10⁵), or PBS, were injected into mice two weeks after unilateral renal artery stenosis (RAS) or sham surgeries (n = 6 each). Fourteen days later, kidneys were harvested and stained with M1 or M2 markers. Lean MSCs decreased macrophages M1 marker intensity, which remained elevated in macrophages co-cultured with obese MSCs. TNF-α levels were four-fold higher in conditioned media collected from obese than from lean MSCs. RAS mouse kidneys were shrunk and showed increased M1 macrophage numbers and inflammatory cytokine expression compared with normal kidneys. Lean MSCs decreased M1 macrophages, M1/M2 ratio and inflammation in RAS kidneys, whereas obese MSCs did not. MSCs isolated from lean human subjects decrease inflammatory M1 macrophages both in vivo and in vitro, an immune-modulatory function which is blunted in MSCs isolated from obese subjects.

中文翻译：

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从肥胖患者中分离的脂肪组织来源的间充质干/基质细胞的免疫调节能力受损

脂肪组织来源的间充质干/基质细胞 (MSCs) 的免疫调节特性可能容易受到代谢紊乱的影响。我们假设 MSCs 的免疫调节功能可能在肥胖的人类受试者中减弱。MSCs 分别在减肥或肾脏捐赠手术期间从肥胖和瘦受试者的腹部皮下脂肪中收集。MSCs 与 M1 巨噬细胞在体外共培养 24 小时，通过流式细胞术确定为 M1 或 M2 表型，并在条件培养基中测量细胞因子。在单侧肾动脉狭窄 (RAS) 或假手术⁽ n = 6 个）。十四天后，收获肾脏并用 M1 或 M2 标记染色。瘦 MSCs 降低了巨噬细胞 M1 标志物的强度，这在与肥胖 MSCs 共培养的巨噬细胞中保持升高。从肥胖收集的条件培养基中的 TNF-α 水平是从瘦 MSCs 收集的四倍。与正常肾脏相比，RAS 小鼠肾脏缩小并显示出增加的 M1 巨噬细胞数量和炎性细胞因子表达。瘦 MSCs 降低了 RAS 肾脏中的 M1 巨噬细胞、M1/M2 比率和炎症，而肥胖的 MSCs 没有。从瘦人受试者中分离出的 MSC 在体内和体外均能减少炎症性 M1 巨噬细胞，这种免疫调节功能在从肥胖受试者中分离出来的 MSC 中减弱。