Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies

Abstract 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-th...

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Main Authors: Xing Hu, Baoqiang Kang, Mingquan Wang, Huaisong Lin, Zhiyong Liu, Zhishuai Zhang, Jiaming Gu, Yuchan Mai, Xinrui Guo, Wanli Ma, Han Yan, Shuoting Wang, Jingxi Huang, Junwei Wang, Jian Zhang, Tianyu Zhang, Bo Feng, Yanling Zhu, Guangjin Pan
Format: Article
Language:English
Published: SpringerOpen 2025-03-01
Series:Cell Regeneration
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Online Access:https://doi.org/10.1186/s13619-025-00227-z
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author Xing Hu
Baoqiang Kang
Mingquan Wang
Huaisong Lin
Zhiyong Liu
Zhishuai Zhang
Jiaming Gu
Yuchan Mai
Xinrui Guo
Wanli Ma
Han Yan
Shuoting Wang
Jingxi Huang
Junwei Wang
Jian Zhang
Tianyu Zhang
Bo Feng
Yanling Zhu
Guangjin Pan
author_facet Xing Hu
Baoqiang Kang
Mingquan Wang
Huaisong Lin
Zhiyong Liu
Zhishuai Zhang
Jiaming Gu
Yuchan Mai
Xinrui Guo
Wanli Ma
Han Yan
Shuoting Wang
Jingxi Huang
Junwei Wang
Jian Zhang
Tianyu Zhang
Bo Feng
Yanling Zhu
Guangjin Pan
author_sort Xing Hu
collection DOAJ
description Abstract 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.
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institution Kabale University
issn 2045-9769
language English
publishDate 2025-03-01
publisher SpringerOpen
record_format Article
series Cell Regeneration
spelling doaj-art-aebb91d2e855404db770ce391b80223d2025-08-20T04:03:03ZengSpringerOpenCell Regeneration2045-97692025-03-0114111410.1186/s13619-025-00227-zHuman induced pluripotent stem cells derived neutrophils display strong anti-microbial potenciesXing Hu0Baoqiang Kang1Mingquan Wang2Huaisong Lin3Zhiyong Liu4Zhishuai Zhang5Jiaming Gu6Yuchan Mai7Xinrui Guo8Wanli Ma9Han Yan10Shuoting Wang11Jingxi Huang12Junwei Wang13Jian Zhang14Tianyu Zhang15Bo Feng16Yanling Zhu17Guangjin Pan18National Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCentre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of SciencesCentre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesThe Third Affiliated Hospital of Sun Yat-Sen UniversityNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesSchool of Biomedical Sciences, Faculty of Medicine, CUHK-GIBH CAS Joint Research Laboratory on Stem Cell and Regenerative Medicine, The Chinese University of Hong KongNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Key Laboratory of Immune Response and Immunotherapy, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1186/s13619-025-00227-zhiPSCsNeutrophilsBacteriaCell therapy
spellingShingle Xing Hu
Baoqiang Kang
Mingquan Wang
Huaisong Lin
Zhiyong Liu
Zhishuai Zhang
Jiaming Gu
Yuchan Mai
Xinrui Guo
Wanli Ma
Han Yan
Shuoting Wang
Jingxi Huang
Junwei Wang
Jian Zhang
Tianyu Zhang
Bo Feng
Yanling Zhu
Guangjin Pan
Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies
Cell Regeneration
hiPSCs
Neutrophils
Bacteria
Cell therapy
title Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies
title_full Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies
title_fullStr Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies
title_full_unstemmed Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies
title_short Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies
title_sort human induced pluripotent stem cells derived neutrophils display strong anti microbial potencies
topic hiPSCs
Neutrophils
Bacteria
Cell therapy
url https://doi.org/10.1186/s13619-025-00227-z
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