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

Autor: Qiang Guo, Jianwei Chen, Jianjian Wu, Zijun Mo, Lei Ye, Wenwen Zhong, Yi Zhang, Huajian Lai, Yifei Zhang, Jianguang Qiu, Tao Xu, Dejuan Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Bioactive Materials, Vol 40, Iss , Pp 649-664 (2024)
Druh dokumentu: article
ISSN: 2452-199X
DOI: 10.1016/j.bioactmat.2024.08.011
Popis: 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 microfiber-derived EVs significantly ameliorate renal UIRI, opening new avenues for effective and efficient EV-based therapies in UIRI treatment.
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