Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Institute of Medical Laboratory Animal Science, CAMS&PUMC; Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing, 100021, China.
Stem Cell Res Ther. 2021 Jul 15;12(1):407. doi: 10.1186/s13287-021-02490-8.
Atherosclerosis (AS) is a complex disease caused in part by dyslipidemia and chronic inflammation. AS is associated with serious cardiovascular disease and remains the leading cause of mortality worldwide. Mesenchymal stem cells (MSCs) have evolved as an attractive therapeutic agent in various diseases including AS. Human umbilical cord MSCs (UCSCs) have been used in cell therapy trials due to their ability to differentiate and proliferate. The present study aimed to investigate the effect of UCSCs treatment on atherosclerotic plaque formation and the progression of lesions in a high-fat diet rabbit model.
Rabbits were fed a high-fat diet and then randomly divided into three groups: control, model, and treatment groups. Rabbits in the treatment group were injected with UCSCs (6 × 10 in 500 μL phosphate buffered saline) after 1 month of high-fat diet, once every 2 weeks, for 3 months. The model group was given PBS only. We analyzed serum biomarkers, used ultrasound and histopathology to detect arterial plaques and laser Doppler imaging to measure peripheral blood vessel blood filling, and analyzed the intestinal flora and metabolism.
Histological analysis showed that the aortic plaque area was significantly reduced in the treatment group. We also found a significant decrease in macrophage accumulation and apoptosis, an increase in expression of scavenger receptors CD36 and SRA1, a decrease in uptake of modified low-density protein (ox-LDL), and a decrease in levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α following UCSCs treatment. We also found that anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β expression increased in the aorta atherosclerotic plaque of the treatment group. UCSCs treatment improved the early peripheral blood filling, reduced the serum lipid level, and inhibited inflammation progression by regulating the intestinal flora dysbiosis caused by the high-fat diet. More specifically, levels of the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) were down-regulated in the treatment group.
UCSCs treatment alleviated atherosclerotic plaque burden by reducing inflammation, regulating the intestinal flora and TMAO levels, and repairing the damaged endothelium.
动脉粥样硬化（AS）是一种由血脂异常和慢性炎症引起的复杂疾病。AS 与严重的心血管疾病有关，仍然是全球死亡的主要原因。间充质干细胞（MSCs）在包括 AS 在内的各种疾病的治疗中已成为一种有吸引力的治疗药物。由于其分化和增殖的能力，人脐带间充质干细胞（UCSC）已被用于细胞治疗试验。本研究旨在探讨 UCSC 治疗对高脂饮食兔模型动脉粥样硬化斑块形成和病变进展的影响。
兔子喂食高脂肪饮食，然后随机分为三组：对照组、模型组和治疗组。治疗组兔子在高脂饮食 1 个月后注射 UCSC（6×10 在 500μL 磷酸盐缓冲液中），每 2 周 1 次，共 3 个月。模型组仅给予 PBS。我们分析了血清生物标志物，使用超声和组织病理学检测动脉斑块，使用激光多普勒成像测量外周血管血液充盈，并分析了肠道菌群和代谢物。
组织学分析显示，治疗组主动脉斑块面积明显减少。我们还发现巨噬细胞积聚和凋亡减少，清道夫受体 CD36 和 SRA1 的表达增加，修饰的低密度脂蛋白（ox-LDL）的摄取减少，促炎细胞因子白细胞介素（IL）-6 和肿瘤坏死因子（TNF）-α的水平降低。我们还发现，抗炎细胞因子 IL-10 和转化生长因子（TGF）-β在治疗组主动脉粥样硬化斑块中的表达增加。UCSC 治疗通过调节高脂肪饮食引起的肠道菌群失调，改善早期外周血液充盈，降低血清脂质水平，并抑制炎症进展。具体而言，治疗组的微生物群依赖性代谢物三甲胺 N-氧化物（TMAO）水平降低。
UCSC 治疗通过减少炎症、调节肠道菌群和 TMAO 水平以及修复受损的内皮细胞，减轻了动脉粥样硬化斑块的负担。
