AUTHOR=Gao Qiuxia , Yan Yan , Zhang Jie , Li Xiaoxue , Wang Jiamei , Feng Yi , Li Peiran , Wang Huanhuan , Zhang Yunlong , He Lingjie , Shan Zhiyan , Li Bin 

TITLE=Autologous cryo-shocked neutrophils enable targeted therapy of sepsis via broad-spectrum neutralization of pro-inflammatory cytokines and endotoxins

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 12 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1359946

DOI=10.3389/fchem.2024.1359946

ISSN=2296-2646

ABSTRACT=Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, in large part owing to the mechanistic complexity of immune regulation and cytokine interactions. Here, we demonstrate a broad spectrum anti-inflammatory and endotoxin neutralization strategy based on autologous "cryo-shocked" neutrophils (CS-Neus) for the management of sepsis. Neutrophils can be frozen to death by a novel liquid nitrogen "cryo-shock" strategy. It is shown that these CS-Neus inherit the source cells membrane structure and functions associated with the inflammatory site targeting, broad-spectrum inflammatory cytokines and endotoxin (LPS) neutralizing.Particularly, this strategy can disable neutrophils of harmful pro-inflammatory functions such as cytokine secretion. Autologous cell-based therapy strategies simultaneously avoid immune rejection and improve treatment safety, making them ideal biomaterials for targeting inflammatory organs for anti-inflammatory. In LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neu ameliorated cytokine storm by removal inflammatory cytokines and endotoxin, showing significant anti-inflammatory therapeutic effects and improved survival rate of mice.