Scale-out production of extracellular vesicles derived from natural killer cells via mechanical stimulation in a seesaw-motion bioreactor for cancer therapy
机构：[1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610065, People’s Republic of China四川大学华西医院[2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, People’s Republic of China[3]Institute for Translational Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310029, People’s Republic of China[4]Endocrine and Metabolic Disease Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Medical Key Laboratory of Hereditary Rare Diseases of Henan[5]Luoyang sub-center of National Clinical Research Center for Metabolic Diseases, Luoyang 471003, People’s Republic of China[5]Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region of China 999077, People’s Republic of China[6]Department of Building Environment and Energy Engineering, Xi’an Jiaotong University, Xian, Shanxi Province 710049, People’s Republic of China[7]Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, United Kingdom[8]State Key Laboratory of Fluid Power and Mechatronic Systems, Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province College of Mechanical Engineering, Zhejiang University, Hangzhou, Zhejiang Province 310029, People’s Republic of China[9]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, People’s Republic of China浙江大学医学院附属第一医院[10]Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, People’s Republic of China[11]Institute for Advanced Study, Chengdu University, Chengdu 610106, People’s Republic of China
Extracellular vesicles (EVs) derived from immune cells have shown great anti-cancer therapeutic potential. However, inefficiency in EV generation has considerably impeded the development of EV-based basic research and clinical translation. Here, we developed a seesaw-motion bioreactor (SMB) system by leveraging mechanical stimuli such as shear stress and turbulence for generating EVs with high quality and quantity from natural killer (NK) cells. Compared to EV production in traditional static culture (229 +/- 74 particles per cell per day), SMB produced NK-92MI-derived EVs at a higher rate of 438 +/- 50 particles per cell per day and yielded a total number of 2 x 10(11) EVs over two weeks via continuous dynamic fluidic culture. In addition, the EVs generated from NK-92MI cells in SMB shared a similar morphology, size distribution, and protein profile to EVs generated from traditional static culture. Most importantly, the NK-92MI-derived EVs in SMB were functionally active in killing melanoma and liver cancer cells in both 2D and 3D culture conditions in vitro, as well as in suppressing melanoma growth in vivo. We believe that SMB is an attractive approach to producing EVs with high quality and quantity; it can additionally enhance EV production from NK92-MI cells and promote both the basic and translational research of EVs.
基金：
Prof. Shuqi Wang would like to acknowledge the
supports from General Program from the National
Natural Science Foundation of China (31871016),
National Key Research and Development Program
(2016YFC1101302), National Key Scientific Instrument
and Equipment Development Projects from
the National Natural Science Foundation of China
(61827806). Prof. Xin Zhao would like to acknowledge
the start-up fund (1-ZE7S), central research
fund (G-YBWS) and intra-faculty fund (1-ZVPC)
from The Hong Kong Polytechnic University. We
also acknowledge the technical support from Mr.
Wangyao Li, Xiaoxiong Zhao, and Jicheng Wu.
第一作者机构：[1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610065, People’s Republic of China[2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, People’s Republic of China[3]Institute for Translational Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310029, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610065, People’s Republic of China[2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, People’s Republic of China[3]Institute for Translational Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310029, People’s Republic of China[11]Institute for Advanced Study, Chengdu University, Chengdu 610106, People’s Republic of China
推荐引用方式(GB/T 7714)：
Wu Jianguo,Wu Di,Wu Guohua,et al.Scale-out production of extracellular vesicles derived from natural killer cells via mechanical stimulation in a seesaw-motion bioreactor for cancer therapy[J].BIOFABRICATION.2022,14(4):doi:10.1088/1758-5090/ac7eeb.
APA：
Wu, Jianguo,Wu, Di,Wu, Guohua,Bei, Ho-Pan,Li, Zihan...&Wang, Shuqi.(2022).Scale-out production of extracellular vesicles derived from natural killer cells via mechanical stimulation in a seesaw-motion bioreactor for cancer therapy.BIOFABRICATION,14,(4)
MLA：
Wu, Jianguo,et al."Scale-out production of extracellular vesicles derived from natural killer cells via mechanical stimulation in a seesaw-motion bioreactor for cancer therapy".BIOFABRICATION 14..4(2022)
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