{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:52:11Z","timestamp":1792122731241,"version":"4.4.0"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["DK120292"],"award-info":[{"award-number":["DK120292"]}]},{"name":"NIH","award":["DK122734"],"award-info":[{"award-number":["DK122734"]}]},{"name":"NIH","award":["HL158691"],"award-info":[{"award-number":["HL158691"]}]},{"name":"NIH","award":["AG062104"],"award-info":[{"award-number":["AG062104"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells14010040","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T07:44:53Z","timestamp":1735803893000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mesenchymal Stem\/Stromal Cells Reverse Adipose Tissue Inflammation in Pigs with Metabolic Syndrome and Renovascular Hypertension"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5229-8264","authenticated-orcid":false,"given":"Alexander B. C.","family":"Krueger","sequence":"first","affiliation":[{"name":"Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2788-5895","authenticated-orcid":false,"given":"Sarosh","family":"Siddiqi","sequence":"additional","affiliation":[{"name":"Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3960-5640","authenticated-orcid":false,"given":"Emma C.","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra L.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Lerman","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-3887","authenticated-orcid":false,"given":"Lilach O.","family":"Lerman","sequence":"additional","affiliation":[{"name":"Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1242\/dmm.001180","article-title":"A comprehensive definition for metabolic syndrome","volume":"2","author":"Huang","year":"2009","journal-title":"Dis. Model. Mech."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"C375","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1161\/HYPERTENSIONAHA.116.08451","article-title":"Role of Perivascular Adipose Tissue in Vascular Physiology and Pathology","volume":"69","author":"Stoffel","year":"2017","journal-title":"Hypertension"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Horwitz, A., and Birk, R. (2023). Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity-The Case of BBS Obesity. Nutrients, 15.","DOI":"10.3390\/nu15153445"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/2231-4040.90879","article-title":"The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases","volume":"2","author":"Tyagi","year":"2011","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1161\/01.RES.0000163635.62927.34","article-title":"Adipose Tissue, Inflammation, and Cardiovascular Disease","volume":"96","author":"Berg","year":"2005","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1111\/eci.12519","article-title":"Adipose tissue and metabolic syndrome: Too much, too little or neither","volume":"45","author":"Grundy","year":"2015","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s11154-014-9301-0","article-title":"Adipocyte dysfunction, inflammation and metabolic syndrome","volume":"15","author":"Kloting","year":"2014","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1038\/s41431-020-0681-1","article-title":"Identification of distinct transcriptome signatures of human adipose tissue from fifteen depots","volume":"28","author":"Schleinitz","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"504","DOI":"10.2337\/dc10-1364","article-title":"Distribution of abdominal visceral and subcutaneous adipose tissue and metabolic syndrome in a Korean population","volume":"34","author":"Kim","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1016\/j.transproceed.2022.05.036","article-title":"High Perirenal Fat Volume Affect Negatively Renal Function in Living Renal Transplantation","volume":"54","author":"Tastemur","year":"2022","journal-title":"Transplant. Proc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.juro.2015.08.105","article-title":"Perirenal Fat Promotes Renal Arterial Endothelial Dysfunction in Obese Swine through Tumor Necrosis Factor-alpha","volume":"195","author":"Ma","year":"2016","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrneph.2016.75","article-title":"Obesity-related glomerulopathy: Clinical and pathologic characteristics and pathogenesis","volume":"12","author":"Chagnac","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"F454","DOI":"10.1152\/ajprenal.00426.2020","article-title":"Mesenchymal stem cells protect renal tubular cells via TSG-6 regulating macrophage function and phenotype switching","volume":"320","author":"Zhao","year":"2021","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_15","first-page":"8965","article-title":"Superimposition of metabolic syndrome magnifies post-stenotic kidney injury in dyslipidemic pigs","volume":"13","author":"Song","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/eurheartj\/ehs197","article-title":"Inflammatory and injury signals released from the post-stenotic human kidney","volume":"34","author":"Eirin","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/j.celrep.2016.07.003","article-title":"Suppression of Resting Metabolism by the Angiotensin AT2 Receptor","volume":"16","author":"Littlejohn","year":"2016","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1440-1797.2007.00764.x","article-title":"Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome","volume":"12","author":"Yilmaz","year":"2007","journal-title":"Nephrology (Carlton)"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12712","DOI":"10.1111\/cpr.12712","article-title":"Immune modulation by mesenchymal stem cells","volume":"53","author":"Jiang","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_20","first-page":"12217","article-title":"Stem cells as a potential therapy in managing various disorders of metabolic syndrome: A systematic review","volume":"13","author":"Shamsuddin","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1089\/scd.2020.0030","article-title":"Mesenchymal Stem\/Stromal Cells and their Extracellular Vesicle Progeny Decrease Injury in Poststenotic Swine Kidney Through Different Mechanisms","volume":"29","author":"Zhao","year":"2020","journal-title":"Stem Cells Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1182\/blood-2010-12-327353","article-title":"Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2\/NF-kappaB signaling in resident macrophages","volume":"118","author":"Choi","year":"2011","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.trsl.2016.12.004","article-title":"The metabolic syndrome and chronic kidney disease","volume":"183","author":"Zhang","year":"2017","journal-title":"Transl. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, H.S., Yi, M.Y., Wu, X., Liu, Q., Deng, Y.H., Wu, T., Wang, L., Kang, Y.X., Luo, X.Q., and Yan, P. (2022). Effects of mesenchymal stem cells in renovascular disease of preclinical and clinical studies: A systematic review and meta-analysis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-23059-2"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1681\/ASN.V1071455","article-title":"Noninvasive evaluation of a novel swine model of renal artery stenosis","volume":"10","author":"Lerman","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ymeth.2008.03.006","article-title":"Adipose-derived stem cells: Isolation, expansion and differentiation","volume":"45","author":"Bunnell","year":"2008","journal-title":"Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/stem.1263","article-title":"Mesenchymal stem cells and endothelial progenitor cells decrease renal injury in experimental swine renal artery stenosis through different mechanisms","volume":"31","author":"Zhu","year":"2013","journal-title":"Stem Cells"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1177\/0963689718780942","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Improve the Renal Microvasculature in Metabolic Renovascular Disease in Swine","volume":"27","author":"Eirin","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"H904","DOI":"10.1152\/ajpheart.00628.2006","article-title":"Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress","volume":"292","author":"Galili","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/B978-0-12-411619-1.00006-9","article-title":"Quantifying size and number of adipocytes in adipose tissue","volume":"537","author":"Parlee","year":"2014","journal-title":"Methods Enzymol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.kint.2016.12.023","article-title":"Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation","volume":"92","author":"Eirin","year":"2017","journal-title":"Kidney Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1080\/14712598.2022.2016695","article-title":"Mechanism of Action of Mesenchymal Stem Cells (MSCs): Impact of delivery method","volume":"22","author":"Bagno","year":"2022","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1172\/JCI129187","article-title":"Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome","volume":"129","author":"Kahn","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Iacobini, C., Vitale, M., Haxhi, J., Menini, S., and Pugliese, G. (2024). Impaired Remodeling of White Adipose Tissue in Obesity and Aging: From Defective Adipogenesis to Adipose Organ Dysfunction. Cells, 13.","DOI":"10.3390\/cells13090763"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/jir.2008.0027","article-title":"Monocyte chemoattractant protein-1 (MCP-1): An overview","volume":"29","author":"Deshmane","year":"2009","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/2047-783X-15-S2-120","article-title":"Proinflammatory cytokines Il-6 and TNF-alpha and the development of inflammation in obese subjects","volume":"15","author":"Popko","year":"2010","journal-title":"Eur. J. Med. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s42255-022-00538-4","article-title":"Interleukin 6 as an energy allocator in muscle tissue","volume":"4","author":"Kistner","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E607","DOI":"10.1152\/ajpendo.00306.2020","article-title":"The controversial role of IL-6 in adipose tissue on obesity-induced dysregulation of glucose metabolism","volume":"319","author":"Wueest","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"25817","DOI":"10.3390\/ijms161025817","article-title":"Interleukins 6 and 15 Levels Are Higher in Subcutaneous Adipose Tissue, but Obesity Is Associated with Their Increased Content in Visceral Fat Depots","volume":"16","author":"Jonas","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gerstner, M., Heller, V., Fechner, J., Hermann, B., Wang, L., and Lausen, J. (2024). Prmt6 represses the pro-adipogenic Ppar-gamma-C\/ebp-alpha transcription factor loop. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-57310-9"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Grigoras, A., Balan, R.A., Caruntu, I.D., Giusca, S.E., Lozneanu, L., Avadanei, R.E., Rusu, A., Riscanu, L.A., and Amalinei, C. (2021). Perirenal Adipose Tissue-Current Knowledge and Future Opportunities. J. Clin. Med., 10.","DOI":"10.3390\/jcm10061291"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Baer, P.C., Koch, B., Hickmann, E., Schubert, R., Cinatl, J., Hauser, I.A., and Geiger, H. (2019). Isolation, Characterization, Differentiation and Immunomodulatory Capacity of Mesenchymal Stromal\/Stem Cells from Human Perirenal Adipose Tissue. Cells, 8.","DOI":"10.3390\/cells8111346"},{"key":"ref_44","first-page":"1972","article-title":"Increased UCP1 expression in the perirenal adipose tissue of patients with renal cell carcinoma","volume":"42","author":"Li","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155080","DOI":"10.1016\/j.cyto.2020.155080","article-title":"Upregulated tumor necrosis factor-alpha transcriptome and proteome in adipose tissue-derived mesenchymal stem cells from pigs with metabolic syndrome","volume":"130","author":"Pawar","year":"2020","journal-title":"Cytokine"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/1\/40\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:22:01Z","timestamp":1759918921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/1\/40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,2]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cells14010040"],"URL":"https:\/\/doi.org\/10.3390\/cells14010040","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,2]]}}}