Bioprinted mesenchymal stem cell microfiber-derived extracellular vesicles alleviate unilateral renal ischemia-reperfusion injury and fibrosis by inhibiting tubular epithelial cells ferroptosis  

作　　者：Qiang Guo Jianwei Chen Jianjian Wu Zijun Mo Lei Ye Wenwen Zhong Yi Zhang Huajian Lai Yifei Zhang Jianguang Qiu Tao Xu Dejuan Wang 

机构地区：[1]Department of Urology,The Sixth Affiliated Hospital,Sun Yat-sen University,No 26 Yuancun Erheng Road,Guangzhou,510655,China [2]Biomedical Innovation Center,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,510655,China [3]Bio-intelligent Manufacturing and Living Matter Bioprinting Center,Research Institute of Tsinghua University in Shenzhen,Tsinghua University,Shenzhen,518057,China [4]Department of Research and Development,Huaqing Zhimei(Shenzhen)Biotechnology Co.,Ltd.,Shenzhen,Guangdong Province,518107,China [5]Tsinghua Shenzhen International Graduate School,Tsinghua University,Shenzhen 518055,China

出　　处：《Bioactive Materials》2024年第10期649-664,共16页生物活性材料（英文）

基　　金：supported by the Natural Science Foundation of China(Grant No.52075285);the Natural Science Foundation of Guang Dong Province(2019A1515010386,2024A1515010266).

摘　　要：Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present substantial potential benefits for renal diseases.However,the limited yield and efficacy of EVs produced through traditional methodologies(2D-EVs)severely restrict their widespread application.Moreover,the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored.In this study,we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology(3D-EVs)with a tail vein injection method,introducing a novel treatment strategy for UIRI.Our comparison of the biological functions of 2D-EVs and 3D-EVs,both in vitro and in vivo,reveals that 3D-EVs significantly outperform 2D-EVs.Specifically,in vitro,3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation(H/R)-induced injuries by reducing epithelial-mesenchymal transformation,extracellular matrix deposition,and ferroptosis.In vivo,3D-EVs exhibit enhanced therapeutic effects,as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys.We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells(TECs)ferroptosis through the modulation of SLC7A11 and GPX4 expression.Our findings suggest that bioprinted mesenchymal stem cells microfiberderived EVs significantly ameliorate renal UIRI,opening new avenues for effective and efficient EV-based therapies in UIRI treatment.

关 键 词：Bioprinted 3D-EVs Unilateral renal ischemia-reperfusion injury KLF15 Ferroptosis 

分 类 号：R318[医药卫生—生物医学工程]