A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments
Abstract Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innova...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47737-z |
| _version_ | 1827277134842822656 |
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| author | Yanmei Zhang Qifan Hu Yuquan Pei Hao Luo Zixuan Wang Xinxin Xu Qing Zhang Jianli Dai Qianqian Wang Zilian Fan Yongcong Fang Min Ye Binhan Li Mailin Chen Qi Xue Qingfeng Zheng Shulin Zhang Miao Huang Ting Zhang Jin Gu Zhuo Xiong |
| author_facet | Yanmei Zhang Qifan Hu Yuquan Pei Hao Luo Zixuan Wang Xinxin Xu Qing Zhang Jianli Dai Qianqian Wang Zilian Fan Yongcong Fang Min Ye Binhan Li Mailin Chen Qi Xue Qingfeng Zheng Shulin Zhang Miao Huang Ting Zhang Jin Gu Zhuo Xiong |
| author_sort | Yanmei Zhang |
| collection | DOAJ |
| description | Abstract Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine. |
| first_indexed | 2024-04-24T07:14:42Z |
| format | Article |
| id | doaj.art-fa3d1c3a662e467eb7331e0cf56a412e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T07:14:42Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-fa3d1c3a662e467eb7331e0cf56a412e2024-04-21T11:22:57ZengNature PortfolioNature Communications2041-17232024-04-0115111710.1038/s41467-024-47737-zA patient-specific lung cancer assembloid model with heterogeneous tumor microenvironmentsYanmei Zhang0Qifan Hu1Yuquan Pei2Hao Luo3Zixuan Wang4Xinxin Xu5Qing Zhang6Jianli Dai7Qianqian Wang8Zilian Fan9Yongcong Fang10Min Ye11Binhan Li12Mailin Chen13Qi Xue14Qingfeng Zheng15Shulin Zhang16Miao Huang17Ting Zhang18Jin Gu19Zhuo Xiong20Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityMOE Key Laboratory of Bioinformatics, BNRIST Bioinformatics Division, Department of Automation, Tsinghua UniversityKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and InstituteBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityMedical School of Chinese PLAInstitute of New Materials and Advanced Manufacturing, Beijing Academy of Science and TechnologyInstitute of New Materials and Advanced Manufacturing, Beijing Academy of Science and TechnologyInstitute of New Materials and Advanced Manufacturing, Beijing Academy of Science and TechnologyBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityDepartment of Radiology, Peking University Cancer Hospital & InstituteDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and InstituteBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityMOE Key Laboratory of Bioinformatics, BNRIST Bioinformatics Division, Department of Automation, Tsinghua UniversityBiomanufacturing Center, Department of Mechanical Engineering, Tsinghua UniversityAbstract Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.https://doi.org/10.1038/s41467-024-47737-z |
| spellingShingle | Yanmei Zhang Qifan Hu Yuquan Pei Hao Luo Zixuan Wang Xinxin Xu Qing Zhang Jianli Dai Qianqian Wang Zilian Fan Yongcong Fang Min Ye Binhan Li Mailin Chen Qi Xue Qingfeng Zheng Shulin Zhang Miao Huang Ting Zhang Jin Gu Zhuo Xiong A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments Nature Communications |
| title | A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments |
| title_full | A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments |
| title_fullStr | A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments |
| title_full_unstemmed | A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments |
| title_short | A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments |
| title_sort | patient specific lung cancer assembloid model with heterogeneous tumor microenvironments |
| url | https://doi.org/10.1038/s41467-024-47737-z |
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