Abstract

Human pluripotent stem cell (hPSC)-induced NK (iNK) cells are a source of off-the-shelf cell products for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryoid body (EB) formation and feeder-based expansion steps, which are time-consuming and cause instability and high costs of manufacturing. Here, we develop an EB-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time-window of 27-day induction, millions of hPSC input can output over billions of iNK cells without the necessity of NK cell expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells via mechanisms of direct cytotoxicity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.

Details

Title
Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells
Author
Huang, Dehao 1 ; Li, Jianhuan 2 ; Hu, Fangxiao 3 ; Xia, Chengxiang 3 ; Weng, Qitong 1 ; Wang, Tongjie 1 ; Peng, Huan 2 ; Wu, Bingyan 2 ; Wu, Hongling 4   VIAFID ORCID Logo  ; Xiong, Jiapin 2 ; Lin, Yunqing 5 ; Wang, Yao 2 ; Zhang, Qi 1   VIAFID ORCID Logo  ; Liu, Xiaofei 4 ; Liu, Lijuan 1 ; Zheng, Xiujuan 2 ; Geng, Yang 4 ; Du, Xin 6 ; Zhu, Xiaofan 7   VIAFID ORCID Logo  ; Wang, Lei 8 ; Hao, Jie 8 ; Wang, Jinyong 9 

1  Chinese Academy of Sciences, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
2  Chinese Academy of Sciences, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Guangzhou, China (GRID:grid.9227.e) (ISNI:0000000119573309); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419) 
3  Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China (GRID:grid.512959.3) 
4  Chinese Academy of Sciences, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Guangzhou, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
5  Chinese Academy of Sciences, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419) 
6  Guangdong General Hospital, Department of Hematology, Guangzhou, China (GRID:grid.413352.2) (ISNI:0000 0004 1760 3705) 
7  Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pediatrics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Tianjin, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
8  Chinese Academy of Sciences, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309); Chinese Academy of Sciences, National Stem Cell Resource Center, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
9  Chinese Academy of Sciences, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China (GRID:grid.512959.3) 
Pages
121
Publication year
2022
Publication date
2022
Publisher
Springer Nature B.V.
e-ISSN
20565968
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41421-022-00467-2
ProQuest document ID
2732910402
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.