Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
Division 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 Korea.
Cells. 2023 Jul 14;12(14):1854. doi: 10.3390/cells12141854.
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 ( = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% ( = 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.
从肺癌患者的手术标本中获得的肺癌类器官（LCO）存在一个主要的挑战。然而，需要化疗的晚期肺癌患者往往无法进行手术。因此，成功地从活检标本中生成 LCO 是当务之急。传统的肺活检技术，如经胸针活检和活检钳活检，只能获得少量的肺组织，导致从活检样本中培养 LCO 的成功率较低。此外，出血和气胸等潜在并发症使得难以获得足够的组织。另一个关键问题是 LCO 培养后期正常肺细胞的过度生长，以及确定 LCO 的最佳培养条件。为了解决这些限制，我们尝试从肺癌患者的冷冻活检标本中创建 LCO（=113）。总体而言，从冷冻活检标本中建立 LCO 的初始成功率为 40.7%（=46）。经支气管冷冻活检可获得比支气管活检钳活检明显更多的肺组织。此外，冷冻活检可用于周围病变，并通过径向支气管内超声辅助进行。本研究显著提高了 LCO 培养的成功率，并证明 LCO 保留了与原发性肿瘤相似的特征。单细胞 RNA 测序证实，源自晚期肺癌患者的 LCO 的早期传代中癌细胞纯度较高。此外，使用三维全断层摄影术对 LCO 的三维结构和细胞内成分进行了表征。最后，使用专门的微柱培养系统对冷冻活检衍生的 LCO 进行了药物筛选。从冷冻活检标本中获得的 LCO 为解决传统 LCO 的关键限制提供了有希望的解决方案。冷冻活检可应用于所有阶段的肺癌患者，包括周围病变患者，并可为 LCO 生成提供足够的细胞。因此，我们预计冷冻活检将成为 LCO 在肺癌所有阶段临床应用的突破性策略。
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