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Mesenchymal stem cells (MSCs) have been shown to stimulate macrophages from M1 phenotype to M2 phenotype. Thus, we aimed to investigate whether the polarization of M1\/M2 induced by MSCs was involved in DN. We injected human umbilical cord MSCs (UC\u2010MSCs) into DN rats and found UC\u2010MSC infusion reduced the infiltration of M1 macrophages and increased the infiltration of M2 macrophages in the glomerulus, thereby attenuating histopathological renal damage and improving renal inflammation and fibrosis in DN rats. Then, peritoneal macrophages were extracted and directed into M1 macrophages by lipopolysaccharides (LPS) in vitro. After coculturing UC\u2010MSCs with M1 macrophages, we found that the M1 macrophage markers and related pro\u2010inflammatory cytokines decreased. However, the expression of the M2 macrophage markers, as well as the anti\u2010inflammatory cytokines, increased observably. Furthermore, UC\u2010MSCs increased the expression of interleukin\u20104 receptor alpha chain (IL\u20104R\u03b1) on macrophages by secreting interleukin\u20106 (IL\u20106); blocking IL\u20106 secretion inhibited the effect of UC\u2010MSCs on M2 macrophage polarization. Then, we explored the mechanism by which M2 macrophages ameliorate DN in vitro and found that UC\u2010MSC\u2010induced M2 macrophages attenuated the secretion of the chemokine monocyte chemoattractant protein\u20101 (MCP\u20101) in hyperglycemia\u2010induced mesangial cells, which led to reduced macrophage recruitment and infiltration. Moreover, UC\u2010MSC\u2010induced M2 macrophages inhibited transforming growth factor \u03b2 (TGF\u2010\u03b2) in glomerular mesangial cells. Our study proposes and discusses a mechanism by which MSCs promote the polarization of macrophages from M1 into M2 in the kidney, thereby ameliorating DN.<\/jats:p>","DOI":"10.1155\/sci\/6684410","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:31:52Z","timestamp":1771479112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mesenchymal Stem Cells Polarize Macrophages to an Anti\u2010Inflammatory Phenotype to Ameliorate Diabetic 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