Respiratory diseases, claim over eight million lives annually. However, the transition from preclinical to clinical phases in research studies is often hindered, partly due to inadequate representation of preclinical models in clinical trials. To address this, we conducted a proof-of-concept study using an ex vivo model to identify lung pathologies and to screen therapeutics in a humanized rodent model. We extracted and decellularized mouse heart-lung tissues using a detergent-based technique. The lungs were then seeded and cultured with human cell lines (BEAS-2B, A549, and Calu3) for 6−10 days, representing healthy lungs, cancerous states, and congenital pathologies, respectively. By manipulating cultural conditions and leveraging the unique characteristics of the cell lines, we successfully modeled various pathologies, including advanced-stage solid tumors and the primary phase of SARS-CoV-2 infection. Validation was conducted through histology, immunofluorescence staining, and pathology analysis. Additionally, our study involved pathological screening of the efficacy and impact of key anti-neoplastic therapeutics (Cisplatin and Wogonin) in cancer models. The results highlight the versatility and strength of the ex vivo model in representing crucial lung pathologies and screening therapeutics during the preclinical phase. This approach holds promise for bridging the gap between preclinical and clinical research, aiding in the development of effective treatments for respiratory diseases, including lung cancer.

中文翻译：

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使用离体生物工程肺来模拟病理学和筛选疗法：概念验证研究


呼吸系统疾病每年夺去超过八百万人的生命。然而，研究中从临床前阶段到临床阶段的过渡常常受到阻碍，部分原因是临床试验中临床前模型的代表性不足。为了解决这个问题，我们使用离体模型进行了概念验证研究，以识别肺部病理并在人源化啮齿动物模型中筛选治疗方法。我们使用基于去污剂的技术提取并脱细胞小鼠心肺组织。然后在肺部接种人类细胞系（BEAS-2B、A549 和 Calu3）并培养 6-10 天，分别代表健康肺部、癌症状态和先天性病变。通过操纵培养条件并利用细胞系的独特特征，我们成功地模拟了各种病理学，包括晚期实体瘤和 SARS-CoV-2 感染的初级阶段。通过组织学、免疫荧光染色和病理学分析进行验证。此外，我们的研究还涉及对癌症模型中关键抗肿瘤治疗药物（顺铂和汉黄芩素）的功效和影响进行病理学筛选。结果强调了离体模型在临床前阶段代表关键肺部病理学和筛选治疗方法方面的多功能性和优势。这种方法有望缩小临床前研究和临床研究之间的差距，有助于开发包括肺癌​​在内的呼吸系统疾病的有效治疗方法。