{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:11:57Z","timestamp":1792163517064,"version":"4.4.0"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2017R1A5A2015385"],"award-info":[{"award-number":["NRF-2017R1A5A2015385"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2022R1A2C2010148"],"award-info":[{"award-number":["NRF-2022R1A2C2010148"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["HR20C0025"],"award-info":[{"award-number":["HR20C0025"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2021-CF-051"],"award-info":[{"award-number":["2021-CF-051"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health and Welfare, the Republic of Korea","award":["NRF-2017R1A5A2015385"],"award-info":[{"award-number":["NRF-2017R1A5A2015385"]}]},{"name":"Ministry of Health and Welfare, the Republic of Korea","award":["NRF-2022R1A2C2010148"],"award-info":[{"award-number":["NRF-2022R1A2C2010148"]}]},{"name":"Ministry of Health and Welfare, the Republic of Korea","award":["HR20C0025"],"award-info":[{"award-number":["HR20C0025"]}]},{"name":"Ministry of Health and Welfare, the Republic of Korea","award":["2021-CF-051"],"award-info":[{"award-number":["2021-CF-051"]}]},{"name":"Korea Disease Control and Prevention Agency and Chungnam National University Hospital","award":["NRF-2017R1A5A2015385"],"award-info":[{"award-number":["NRF-2017R1A5A2015385"]}]},{"name":"Korea Disease Control and Prevention Agency and Chungnam National University Hospital","award":["NRF-2022R1A2C2010148"],"award-info":[{"award-number":["NRF-2022R1A2C2010148"]}]},{"name":"Korea Disease Control and Prevention Agency and Chungnam National University Hospital","award":["HR20C0025"],"award-info":[{"award-number":["HR20C0025"]}]},{"name":"Korea Disease Control and Prevention Agency and Chungnam National University Hospital","award":["2021-CF-051"],"award-info":[{"award-number":["2021-CF-051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.<\/jats:p>","DOI":"10.3390\/cells12141854","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T08:35:47Z","timestamp":1689323747000},"page":"1854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7329-1724","authenticated-orcid":false,"given":"Dongil","family":"Park","sequence":"first","affiliation":[{"name":"Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2776-8146","authenticated-orcid":false,"given":"Dahye","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9028-0872","authenticated-orcid":false,"given":"Yoonjoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonhee","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6173-2748","authenticated-orcid":false,"given":"Jeong Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8873-0021","authenticated-orcid":false,"given":"Min-Kyung","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Woong","family":"Kang","sequence":"additional","affiliation":[{"name":"Thoracic and Cardiovascular Surgery, School of Medicine, Chungnam National University, Munhwa-ro 282, Jung-Gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1935-2140","authenticated-orcid":false,"given":"Yooyoung","family":"Chong","sequence":"additional","affiliation":[{"name":"Thoracic and Cardiovascular Surgery, School of Medicine, Chungnam National University, Munhwa-ro 282, Jung-Gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7361-9993","authenticated-orcid":false,"given":"Sung Joon","family":"Han","sequence":"additional","affiliation":[{"name":"Thoracic and Cardiovascular Surgery, School of Medicine, Chungnam National University, Munhwa-ro 282, Jung-Gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwook","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Life Science, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Koh","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-5628","authenticated-orcid":false,"given":"Jaehyeok","family":"Lee","sequence":"additional","affiliation":[{"name":"Tomocube Inc., Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0528-6661","authenticated-orcid":false,"given":"YongKeun","family":"Park","sequence":"additional","affiliation":[{"name":"Tomocube Inc., Daejeon 34141, Republic of Korea"},{"name":"Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of 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