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

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Bioactive Materials 2024年第10期40卷 649-664页

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 department of Urology The Sixth Affiliated HospitalSun Yat-sen UniversityNo 26 Yuancun Erheng RoadGuangzhou510655China Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou510655China Bio-intelligent Manufacturing and Living Matter Bioprinting Center Research Institute of Tsinghua University in ShenzhenTsinghua UniversityShenzhen518057China department of Research and development Huaqing Zhimei(Shenzhen)Biotechnology Co.Ltd.ShenzhenGuangdong Province518107China Tsinghua Shenzhen International Graduate School Tsinghua UniversityShenzhen 518055China

Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal *** vesicles(evs)present substantial potential benefits for renal ***,the limited yield and efficacy of evs produced through traditional methodologies(2d-evs)severely restrict their widespread ***,the efficient and effective strategies for using evs in UIRI treatment and their mechanisms remain largely *** 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 *** comparison of the biological functions of 2d-evs and 3d-evs,both in vitro and in vivo,reveals that 3d-evs significantly outperform ***,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 *** vivo,3d-evs exhibit enhanced therapeutic effects,as evidenced by improved renal function and decreased collagen deposition in UIRI mouse *** 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 *** 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

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