Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice  

作　　者：Luo-xing Xia Ying-ying Xiao Wen-jing Jiang Xiang-yu Yang Hua Tao Safur Rehman Mandukhail Jian-feng Qin Qian-rong Pan Yu-guang Zhu Li-xin Zhao Li-juan Huang Zhan Li Xi-yong Yu 

机构地区：[1]The Fifth Affiliated Hospital,Key Laboratory of Molecular Target&Clinical Pharmacology,the NMPA and State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences,Guangzhou Medical University,Guangzhou,511436,China

出　　处：《Acta Pharmacologica Sinica》2024年第8期1644-1659,共16页中国药理学报（英文版）

基　　金：supported by the National Key Research and Development Program of China under grant(2022YFE0209700 to Xi-yong Yu);Guangdong Provincial Drug Administration Science and Technology Innovation Project-Key Technology Research on Chest Disease Prevention and Treatment Drug Research and Clinical Evaluation(Grant NO.2022ZDZ10 to Xi-yong Yu);the fellowship of China Postdoctoral Science Foundation(2022M710890 to YYX);the Epigenetic Drug R&D and Cultivation Plan of the School of Pharmacy,Guangzhou Medical University(06-410-2107211 to YYX).

摘　　要：Cardiopulmonary progenitor cells(CPPs)constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth.This fact offers the possibility for the treatment of pulmonary heart disease(PHD),in which the lung and heart are both damaged.A reliable source of CPPs is urgently needed.In this study,we reprogrammed human cardiac fibroblasts(HCFs)into CPP-like cells(or induced CPPs,iCPPs)and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury(ALI).iCPPs were created in passage 3 primary HCFs by overexpressing GLI1,WNT2,ISL1 and TBX5(GWIT).Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs.A mouse ALI model was established by intratracheal instillation of LPS.Four hours after LPS instillation,ALI mice were treated with GWIT-iCPP-derived exosomes(5×10^(9),5×10^(10)particles/mL)via intratracheal instillation.We showed that GWIT-iCPPs could differentiate into cell lineages,such as cardiomyocyte-like cells,endothelial cells,smooth muscle cells and alveolar epithelial cells,in vitro.Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development.Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation,promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier.This study provides a potential new method for the prevention and treatment of cardiopulmonary injury,especially lung injury,and provides a new cell model for drug screening.

关 键 词：acute lung injury cardiopulmonary progenitor cells REPROGRAMMING Tbx5 EXOSOMES 

分 类 号：R563[医药卫生—呼吸系统]