Mesenchymal Stem/Stromal Cells Reverse Adipose Tissue Inflammation in Pigs with Metabolic Syndrome and Renovascular Hypertension

间充质干细胞/基质细胞逆转患有代谢综合征和肾血管性高血压的猪的脂肪组织炎症

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作者:Alexander B C Krueger, Xiangyang Zhu, Sarosh Siddiqi, Emma C Whitehead, Hui Tang, Kyra L Jordan, Amir Lerman, Lilach O Lerman

Abstract

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 (107 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.

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