Krueger Alexander B C, Zhu Xiangyang, Siddiqi Sarosh, Whitehead Emma C, Tang Hui, Jordan Kyra L, Lerman Amir, Lerman Lilach O
Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.
Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.
Cells. 2025 Jan 2;14(1):40. doi: 10.3390/cells14010040.
Metabolic syndrome (MetS) is associated with low-grade inflammation, which can be exacerbated by renal artery stenosis (RAS) and renovascular hypertension, potentially worsening outcomes through pro-inflammatory cytokines. This study investigated whether mesenchymal stem/stromal cells (MSCs) could reduce fat inflammation in pigs with MetS and RAS. Twenty-four pigs were divided into Lean (control), MetS, MetS + RAS, and MetS + RAS + MSCs. In the MSC-treated group, autologous adipose-derived MSCs (10 cells) were injected into the renal artery six weeks after RAS induction. After four weeks, fat volumes and inflammatory markers were assessed. MSC treatment reduced levels of pro-inflammatory cytokines (MCP-1, TNF-a, IL-6) in the renal vein blood and in perirenal fat. The MSCs also decreased fat fibrosis, restored adipocyte size, and altered adipogenesis-related gene expression, particularly in the perirenal fat. These effects were less pronounced in subcutaneous fat. The MSC therapy attenuated fat inflammation and improved metabolic outcomes in pigs with MetS + RAS, suggesting that adipose-derived MSCs may offer a promising therapeutic approach for metabolic disorders.
代谢综合征(MetS)与低度炎症相关,肾动脉狭窄(RAS)和肾血管性高血压会加剧这种炎症,通过促炎细胞因子可能会使病情恶化。本研究调查了间充质干/基质细胞(MSCs)是否能减轻患有MetS和RAS的猪的脂肪炎症。24头猪被分为瘦肉型(对照)、MetS、MetS + RAS以及MetS + RAS + MSCs组。在MSC治疗组中,在诱导RAS六周后将自体脂肪来源的MSCs(10个细胞)注入肾动脉。四周后,评估脂肪体积和炎症标志物。MSC治疗降低了肾静脉血和肾周脂肪中促炎细胞因子(MCP-1、TNF-α、IL-6)的水平。MSCs还减少了脂肪纤维化,恢复了脂肪细胞大小,并改变了脂肪生成相关基因的表达,特别是在肾周脂肪中。这些作用在皮下脂肪中不太明显。MSC疗法减轻了患有MetS + RAS的猪的脂肪炎症并改善了代谢结果,表明脂肪来源的MSCs可能为代谢紊乱提供一种有前景的治疗方法。