Hu Xing, Kang Baoqiang, Wang Mingquan, Lin Huaisong, Liu Zhiyong, Zhang Zhishuai, Gu Jiaming, Mai Yuchan, Guo Xinrui, Ma Wanli, Yan Han, Wang Shuoting, Huang Jingxi, Wang Junwei, Zhang Jian, Zhang Tianyu, Feng Bo, Zhu Yanling, Pan Guangjin
National Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Cell Regen. 2025 Mar 21;14(1):8. doi: 10.1186/s13619-025-00227-z.
Neutrophils are essential innate immune cells with unusual anti-microbial properties while dysfunctions of neutrophils lead to severe health problems such as lethal infections. Generation of neutrophils from human induced pluripotent stem cells (hiPSCs) is highly promising to produce off-the-shelf neutrophils for transfusion therapies. However, the anti-microbial potencies of hiPSCs derived neutrophils (iNEUs) remain less documented. Here, we develop a scalable approach to generate iNEUs in a chemical defined condition. iNEUs display typical neutrophil characters in terms of phagocytosis, migration, formation of neutrophil extracellular traps (NETs), etc. Importantly, iNEUs display a strong killing potency against various bacteria such as K.pneumoniae, P.aeruginosa, E.coli and S.aureus. Moreover, transfusions of iNEUs in mice with neutrophil dysfunction largely enhance their survival in lethal infection of different bacteria. Together, our data show that hiPSCs derived neutrophils hold strong anti-microbial potencies to protect severe infections under neutrophil dysfunction conditions.
中性粒细胞是具有独特抗菌特性的重要先天性免疫细胞，而中性粒细胞功能障碍会导致严重的健康问题，如致命感染。从人诱导多能干细胞（hiPSC）生成中性粒细胞对于生产用于输血治疗的现成中性粒细胞非常有前景。然而，hiPSC衍生的中性粒细胞（iNEU）的抗菌能力仍缺乏充分记录。在此，我们开发了一种可扩展的方法，在化学定义的条件下生成iNEU。iNEU在吞噬作用、迁移、中性粒细胞胞外陷阱（NET）形成等方面表现出典型的中性粒细胞特征。重要的是，iNEU对多种细菌如肺炎克雷伯菌、铜绿假单胞菌、大肠杆菌和金黄色葡萄球菌具有强大的杀伤能力。此外，将iNEU输注到中性粒细胞功能障碍的小鼠体内，在很大程度上提高了它们在不同细菌致命感染中的存活率。总之，我们的数据表明，hiPSC衍生的中性粒细胞在中性粒细胞功能障碍条件下具有强大的抗菌能力以保护免受严重感染。
