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Disease-derived circulating extracellular vesicle preconditioning:A promising strategy for precision mesenchymal stem cell therapy

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Acta Pharmaceutica Sinica B 2024年第10期14卷 4526-4543页

作者： Ke Lv Tian Wu Shuyun Liu Peng Lou Pingya Zhou Yizhuo Wang Xiyue Zhou Shu Zhang Dan Du Yanrong Lu Meihua Wan Jingping Liu Department of Integrated Traditional Chinese and Western Medicine and NHC Key Laboratory of Transplant Engineering and Immunology Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Department of Emergency Medicine Emergency Medical LaboratoryWest China HospitalSichuan UniversityChengdu 610041China Advanced Mass Spectrometry Center Research Core FacilityFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China West China Center of Excellence for Pancreatitis Institute of Integrated Traditional Chinese and Western MedicineWest China HospitalSichuan UniversityChengdu 610041China The First People’s Hospital of Shuangliu District Chengdu 610299China

Mesenchymal stem cell(MSC)-based therapies have emerged as promising methods for regenerative medicine;however,how to precisely enhance their tissue repair effects is still a major question in the *** extracellular vesicles(EVs)from diseased states carry diverse pathological information and affect the functions of recipient *** on this unique property,we report that disease-derived circulating EV(disease-EV)preconditioning is a potent strategy for precisely enhancing the tissue repair potency of MSCs in diverse disease ***,plasma EVs from lung or kidney tissue injuries were shown to contain distinctly enriched molecules and were shown to induce tissue injury-specific gene expression responses in cultured ***-EV preconditioning improved the performance(including proliferation,migration,and growth factor production)of MSCs through metabolic reprogramming(such as via enhanced oxidative phosphorylation and lipid metabolism)without inducing an adverse immune ***,compared with normal MSCs,disease-EV-preconditioned MSCs exhibited superior tissue repair effects(including anti-inflammatory and antiapoptotic effects)in diverse types of tissue injury(such as acute lung or kidney injury).Disease-derived EVs may serve as a type of“off-the-shelf”product due to multiple advantages,such as flexibility,stability,long-term storage,and ease of shipment and *** study highlights the idea that disease-EV preconditioning is a robust strategy for precisely enhancing the regenerative capacity of MSC-based therapies.

关键词： Regenerative medicine Mesenchymal stem cell circulating extracellular vesicle Tissue injury Metabolic reprogramming Inflammation Cell death Preconditioning

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