Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids
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...
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MDPI AG
2023-07-01
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| author | Dongil Park Dahye Lee Yoonjoo Kim Yeonhee Park Yeon-Jae Lee Jeong Eun Lee Min-Kyung Yeo Min-Woong Kang Yooyoung Chong Sung Joon Han Jinwook Choi Jong-Eun Park Yongjun Koh Jaehyeok Lee YongKeun Park Ryul Kim Jeong Seok Lee Jimin Choi Sang-Hyun Lee Bosung Ku Da Hyun Kang Chaeuk Chung |
| author_facet | Dongil Park Dahye Lee Yoonjoo Kim Yeonhee Park Yeon-Jae Lee Jeong Eun Lee Min-Kyung Yeo Min-Woong Kang Yooyoung Chong Sung Joon Han Jinwook Choi Jong-Eun Park Yongjun Koh Jaehyeok Lee YongKeun Park Ryul Kim Jeong Seok Lee Jimin Choi Sang-Hyun Lee Bosung Ku Da Hyun Kang Chaeuk Chung |
| author_sort | Dongil Park |
| collection | DOAJ |
| description | 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 (<i>n</i> = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (<i>n</i> = 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. |
| first_indexed | 2024-03-11T01:12:23Z |
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| language | English |
| last_indexed | 2024-03-11T01:12:23Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-29851c3eaa914ca6810b4b1723a5cb8a2023-11-18T18:46:07ZengMDPI AGCells2073-44092023-07-011214185410.3390/cells12141854Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer OrganoidsDongil Park0Dahye Lee1Yoonjoo Kim2Yeonhee Park3Yeon-Jae Lee4Jeong Eun Lee5Min-Kyung Yeo6Min-Woong Kang7Yooyoung Chong8Sung Joon Han9Jinwook Choi10Jong-Eun Park11Yongjun Koh12Jaehyeok Lee13YongKeun Park14Ryul Kim15Jeong Seok Lee16Jimin Choi17Sang-Hyun Lee18Bosung Ku19Da Hyun Kang20Chaeuk Chung21Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 34943, Republic of KoreaDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDepartment of Pathology, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaThoracic and Cardiovascular Surgery, School of Medicine, Chungnam National University, Munhwa-ro 282, Jung-Gu, Daejeon 35015, Republic of KoreaThoracic and Cardiovascular Surgery, School of Medicine, Chungnam National University, Munhwa-ro 282, Jung-Gu, Daejeon 35015, Republic of KoreaThoracic and Cardiovascular Surgery, School of Medicine, Chungnam National University, Munhwa-ro 282, Jung-Gu, Daejeon 35015, Republic of KoreaSchool of Life Science, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of KoreaTomocube Inc., Daejeon 34141, Republic of KoreaTomocube Inc., Daejeon 34141, Republic of KoreaGENOME INSIGHT Inc., Daejeon 34051, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of KoreaCentral R&D Center, Medical & Bio Decision Co., Ltd., Suwon 16229, Republic of KoreaCentral R&D Center, Medical & Bio Decision Co., Ltd., Suwon 16229, Republic of KoreaCentral R&D Center, Medical & Bio Decision Co., Ltd., Suwon 16229, Republic of KoreaDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaOne 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 (<i>n</i> = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (<i>n</i> = 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.https://www.mdpi.com/2073-4409/12/14/1854cryobiopsylung cancerorganoidhigh cancer cell puritythree-dimensional holotomographydrug screening |
| spellingShingle | Dongil Park Dahye Lee Yoonjoo Kim Yeonhee Park Yeon-Jae Lee Jeong Eun Lee Min-Kyung Yeo Min-Woong Kang Yooyoung Chong Sung Joon Han Jinwook Choi Jong-Eun Park Yongjun Koh Jaehyeok Lee YongKeun Park Ryul Kim Jeong Seok Lee Jimin Choi Sang-Hyun Lee Bosung Ku Da Hyun Kang Chaeuk Chung Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids Cells cryobiopsy lung cancer organoid high cancer cell purity three-dimensional holotomography drug screening |
| title | Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids |
| title_full | Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids |
| title_fullStr | Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids |
| title_full_unstemmed | Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids |
| title_short | Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids |
| title_sort | cryobiopsy a breakthrough strategy for clinical utilization of lung cancer organoids |
| topic | cryobiopsy lung cancer organoid high cancer cell purity three-dimensional holotomography drug screening |
| url | https://www.mdpi.com/2073-4409/12/14/1854 |
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