Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics
Abstract Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient‐specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treat...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202206603 |
| _version_ | 1797812783791734784 |
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| author | Ming‐You Shie Hsin‐Yuan Fang Kai‐Wen Kan Chia‐Che Ho Chih‐Yen Tu Pei‐Chih Lee Po‐Ren Hsueh Chia‐Hung Chen Alvin Kai‐Xing Lee Ni Tien Jian‐Xun Chen Yu‐Cheng Shen Jan‐Gowth Chang Yu‐Fang Shen Ting‐Ju Lin Ben Wang Mien‐Chie Hung Der‐Yang Cho Yi‐Wen Chen |
| author_facet | Ming‐You Shie Hsin‐Yuan Fang Kai‐Wen Kan Chia‐Che Ho Chih‐Yen Tu Pei‐Chih Lee Po‐Ren Hsueh Chia‐Hung Chen Alvin Kai‐Xing Lee Ni Tien Jian‐Xun Chen Yu‐Cheng Shen Jan‐Gowth Chang Yu‐Fang Shen Ting‐Ju Lin Ben Wang Mien‐Chie Hung Der‐Yang Cho Yi‐Wen Chen |
| author_sort | Ming‐You Shie |
| collection | DOAJ |
| description | Abstract Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient‐specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient‐derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung‐cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co‐clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care. |
| first_indexed | 2024-03-13T07:43:34Z |
| format | Article |
| id | doaj.art-353e98e316a144529d9d5503d9b62a14 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T07:43:34Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-353e98e316a144529d9d5503d9b62a142023-06-03T01:03:32ZengWileyAdvanced Science2198-38442023-06-011016n/an/a10.1002/advs.202206603Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision TherapeuticsMing‐You Shie0Hsin‐Yuan Fang1Kai‐Wen Kan2Chia‐Che Ho3Chih‐Yen Tu4Pei‐Chih Lee5Po‐Ren Hsueh6Chia‐Hung Chen7Alvin Kai‐Xing Lee8Ni Tien9Jian‐Xun Chen10Yu‐Cheng Shen11Jan‐Gowth Chang12Yu‐Fang Shen13Ting‐Ju Lin14Ben Wang15Mien‐Chie Hung16Der‐Yang Cho17Yi‐Wen Chen18School of Dentistry China Medical University Taichung 406040 Taiwanx‐Dimension Center for Medical Research and Translation China Medical University Hospital Taichung 404332 Taiwanx‐Dimension Center for Medical Research and Translation China Medical University Hospital Taichung 404332 TaiwanDepartment of Bioinformatics and Medical Engineering Asia University Taichung 41354 TaiwanSchool of Medicine China Medical University Taichung City 40447 TaiwanGraduate Institute of Biomedical Sciences China Medical University Taichung City 406040 TaiwanSchool of Medicine China Medical University Taichung City 40447 TaiwanSchool of Medicine China Medical University Taichung City 40447 TaiwanSchool of Medicine China Medical University Taichung City 40447 TaiwanDepartment of Laboratory Medicine China Medical University Hospital Taichung City 404332 TaiwanDepartment of Thoracic Surgery China Medical University Hospital Taichung City 40447 TaiwanDepartment of Thoracic Surgery China Medical University Hospital Taichung City 40447 TaiwanCenter for Precision Medicine China Medical University Hospital Taichung City 404332 TaiwanDepartment of Bioinformatics and Medical Engineering Asia University Taichung 41354 TaiwanGraduate Institute of Biomedical Sciences China Medical University Taichung City 406040 TaiwanH. Milton Stewart School of Industrial and System Engineering Georgia Institute of Technology 755 Ferst Dr NW Atlanta GA 30332 USAGraduate Institute of Biomedical Sciences China Medical University Taichung City 406040 TaiwanGraduate Institute of Biomedical Sciences China Medical University Taichung City 406040 Taiwanx‐Dimension Center for Medical Research and Translation China Medical University Hospital Taichung 404332 TaiwanAbstract Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient‐specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient‐derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung‐cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co‐clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.https://doi.org/10.1002/advs.202206603decellularized extracellular matrixlung spheroid modelprecision medicinetumor microenvironment |
| spellingShingle | Ming‐You Shie Hsin‐Yuan Fang Kai‐Wen Kan Chia‐Che Ho Chih‐Yen Tu Pei‐Chih Lee Po‐Ren Hsueh Chia‐Hung Chen Alvin Kai‐Xing Lee Ni Tien Jian‐Xun Chen Yu‐Cheng Shen Jan‐Gowth Chang Yu‐Fang Shen Ting‐Ju Lin Ben Wang Mien‐Chie Hung Der‐Yang Cho Yi‐Wen Chen Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics Advanced Science decellularized extracellular matrix lung spheroid model precision medicine tumor microenvironment |
| title | Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics |
| title_full | Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics |
| title_fullStr | Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics |
| title_full_unstemmed | Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics |
| title_short | Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics |
| title_sort | highly mimetic ex vivo lung cancer spheroid based physiological model for clinical precision therapeutics |
| topic | decellularized extracellular matrix lung spheroid model precision medicine tumor microenvironment |
| url | https://doi.org/10.1002/advs.202206603 |
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