Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Through the Promotion of Type 2 Macrophage Polarization.

Stem cells and development Pub Date : 2025-06-01 Epub Date: 2025-05-26 DOI:10.1089/scd.2025.0038
Xia Zhu, Yinghao Wang, Zhenquan Sun, Wei Cheng, Kexin Chen, Xiao Gao, Jing Meng, Suyan Li, Wen Zheng, Yang Wang, Xiaoxing Yin, Xueyan Zhou
{"title":"Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Through the Promotion of Type 2 Macrophage Polarization.","authors":"Xia Zhu, Yinghao Wang, Zhenquan Sun, Wei Cheng, Kexin Chen, Xiao Gao, Jing Meng, Suyan Li, Wen Zheng, Yang Wang, Xiaoxing Yin, Xueyan Zhou","doi":"10.1089/scd.2025.0038","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetic nephropathy (DN), recognized as the leading cause of end-stage renal disease globally, necessitates novel therapeutic development. While mesenchymal stromal cells (MSCs) demonstrate therapeutic potential in DN management, their precise mechanisms require systematic elucidation. This study investigated the link between DN and inflammation activation, as well as the pathophysiological significance of MSC-mediated macrophage polarization and podocyte injury repair during this progression. We administered MSCs to streptozotocin-induced diabetic rats via tail vein injection and co-cultured podocytes and MSCs under high-glucose (HG) conditions. Subsequently, we assessed M2-like macrophage polarization and inflammation levels both in vitro and in vivo. In addition, we observed the distribution and homing of MSCs in vivo through <sup>89</sup>Zr labeling. Our results revealed that HG increased podocyte apoptosis and inflammation in both podocyte and diabetic rats. Treatment with MSCs attenuated inflammation, promoted M2-like macrophage polarization in podocyte under HG conditions as well as in diabetic rats, ultimately ameliorating kidney injury. Importantly, it was observed that MSCs homed to the kidney of DN rats, thereby exerting their therapeutic effects. Collectively, our findings demonstrate that MSCs exhibit renal homing capacity in diabetic kidney and protect podocytes from inflammation by promoting M2 macrophage polarization, thereby establishing MSCs as a promising therapeutic cell-free strategy for DN.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"258-270"},"PeriodicalIF":0.0000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem cells and development","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/scd.2025.0038","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/26 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Diabetic nephropathy (DN), recognized as the leading cause of end-stage renal disease globally, necessitates novel therapeutic development. While mesenchymal stromal cells (MSCs) demonstrate therapeutic potential in DN management, their precise mechanisms require systematic elucidation. This study investigated the link between DN and inflammation activation, as well as the pathophysiological significance of MSC-mediated macrophage polarization and podocyte injury repair during this progression. We administered MSCs to streptozotocin-induced diabetic rats via tail vein injection and co-cultured podocytes and MSCs under high-glucose (HG) conditions. Subsequently, we assessed M2-like macrophage polarization and inflammation levels both in vitro and in vivo. In addition, we observed the distribution and homing of MSCs in vivo through 89Zr labeling. Our results revealed that HG increased podocyte apoptosis and inflammation in both podocyte and diabetic rats. Treatment with MSCs attenuated inflammation, promoted M2-like macrophage polarization in podocyte under HG conditions as well as in diabetic rats, ultimately ameliorating kidney injury. Importantly, it was observed that MSCs homed to the kidney of DN rats, thereby exerting their therapeutic effects. Collectively, our findings demonstrate that MSCs exhibit renal homing capacity in diabetic kidney and protect podocytes from inflammation by promoting M2 macrophage polarization, thereby establishing MSCs as a promising therapeutic cell-free strategy for DN.

间充质干细胞通过促进2型巨噬细胞极化减轻糖尿病肾病足细胞损伤。
糖尿病肾病(DN)是全球公认的终末期肾脏疾病的主要原因,需要开发新的治疗方法。虽然间充质间质细胞(MSCs)在DN治疗中显示出治疗潜力,但其确切机制需要系统的阐明。本研究探讨了DN与炎症激活的关系,以及在此过程中msc介导的巨噬细胞极化和足细胞损伤修复的病理生理意义。我们通过尾静脉注射给链脲佐菌素诱导的糖尿病大鼠注入MSCs,并在高糖(HG)条件下共培养足细胞和MSCs。随后,我们评估了体内和体外的m2样巨噬细胞极化和炎症水平。此外,我们还通过89Zr标记观察了MSCs在体内的分布和归巢。我们的研究结果显示,HG增加足细胞凋亡和糖尿病大鼠的炎症。MSCs治疗可减轻炎症,促进HG和糖尿病大鼠足细胞中m2样巨噬细胞极化,最终改善肾损伤。重要的是,观察到MSCs在DN大鼠的肾脏中归巢,从而发挥其治疗作用。总之,我们的研究结果表明,MSCs在糖尿病肾脏中表现出肾脏归巢能力,并通过促进M2巨噬细胞极化来保护足细胞免受炎症,从而确立了MSCs作为一种有前途的无细胞治疗DN策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信