Introduction: Metabolic Syndrome (MetS) is a constellation of risk factors including glucose intolerance, central obesity, hypertension, and dyslipidemia. Low-grade inflammation, possibly originating in inflamed fat, has been implicated in the genesis and pathophysiological consequences of MetS. MetS occasionally co-exists with renal artery stenosis (RAS) and aggravates outcomes partly through the release of pro-inflammatory cytokines. Mesenchymal stem/stromal cells (MSCs) are multipotent cells with robust regenerative and immunomodulatory potential. This study tested the hypothesis that MSC delivery would alternate fat inflammation in MetS+RAS.
Methods: Twenty-four pigs were randomly divided into four groups: Lean, MetS, MetS+RAS, and Mets+RAS+MSC (n=6 each). In MetS+RAS+MSC pigs autologous adipose tissue-derived MSCs (107) were injected into the renal artery 6 weeks after RAS induction. Four weeks later, renal function was studied in-vivo using CT. After euthanasia, adipose tissue samples were stained to assess inflammatory markers, regulatory T-cells, resident stem cells, T-bet+ B-cells, adipocyte size, and fat fibrosis. Pro-inflammatory monocyte chemoattractant protein-1 (MCP-1), interleukin-6, and tumor necrosis factor-alpha immunoreactivity and levels were measured in fat and systemic blood, respectively.
Results: Injection of MSCs into MetS+RAS pigs did not affect renal function but slightly decreased blood pressure and circulating MCP-1 levels in systemic blood. Furthermore, in subcutaneous adipose tissue MSCs restored T-regulatory cells and endogenous stem cells, decreased T-bet+ B-cells, and downregulated inflammatory marker immunoreactivity. MSCs also restored adipocyte size and reduced fat fibrosis. 
Conclusion: Adipose tissue-derived MSCs attenuate fat inflammation in pigs with MetS+RAS. Hence, MSCs may represent a promising therapeutic strategy in metabolic disorders.

Mesenchymal Stem Cells Reverse Inflammatory Changes in the Adipose Tissue of Swine with Metabolic Syndrome and Renovascular Hypertension

 Nephrology

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Mesenchymal Stem Cells Reverse Inflammatory Changes in the Adipose Tissue of Swine with Metabolic Syndrome and Renovascular Hypertension

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