Nitric oxide-mediated the therapeutic properties of induced pluripotent stem cell for paraquat-induced acute lung injury

Frontiers in Immunology

Immunology

Xuemeng Wang¹  Yijun Li¹  Sifeng Chen¹  Shirui Li¹  Fuchen Chen¹  Anfeng Cui²  Meng Xiang³  Jiongwei Huang⁴  Dawei Yang⁵  Nana Song⁶ 

[1] Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;Department of Pathology, The Second Clinical Medical College, Shanxi Medical University, Taiyuan, China;Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;Fudan Zhang Jiang Institute, Shanghai, China;Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China;Health Management Center Department, Zhongshan Hospital, Fudan University, Shanghai, China;Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai, China;Fudan Zhang Jiang Institute, Shanghai, China;

关键词: induced pluripotent stem cell;    nitric oxide;    acute lung injury;    L-arginine;    L-NAME;   

DOI  :  10.3389/fimmu.2023.1136290

 received in 2023-01-10, accepted in 2023-05-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

The mortality rate associated with acute lung injury (ALI) and its severe form, acute respiratory distress syndrome, is high. Induced pluripotent stem cell (iPSC) therapy is a potential treatment method for ALI, but its therapeutic efficacy is limited in injured lungs. Nitric oxide (NO) has various physiological actions. The current study investigated the effect of iPSCs pretreated with NO donors in paraquat (PQ)-induced ALI mouse model. Male C57BL/6 mice were intraperitoneally injected with PQ, followed by infusion of phosphate-buffered saline, iPSCs, L-arginine pretreated iPSCs, or Nitro-L-arginine methylester (L-NAME) pretreated iPSCs through the tail veins. Histopathological changes, pulmonary microvascular permeability, and inflammatory cytokine levels were analyzed after 3 or 28 d. The effects on iPSC proliferation, migration, and adhesion were evaluated in vitro. More L-arginine-pretreated iPSCs were selectively trafficked into the injured pulmonary tissue of mice with LPS-induced ALI, drastically diminishing the histopathologic changes and inflammatory cytokine levels (IL-1β and IL-6). There was also markedly improved pulmonary microvascular permeability and pulmonary function. The NO inhibitor abolished the protective effects of iPSCs. In addition, the ability of L-arginine to promote the proliferation and migration of iPSCs was decreased by L-NAME pretreatment, suggesting that NO might mediate the therapeutic benefits of iPSC. The improvement of the iPSC physiological changes by the endogenous gaseous molecule NO reduces lung injury severity. L-Arginine represents a pharmacologically important strategy for enhancing the therapeutic potential of iPSCs.

【 授权许可】

Unknown   
Copyright © 2023 Cui, Li, Li, Yang, Huang, Wang, Song, Chen, Chen and Xiang