Wang Heping, Han Zhiyi, Yang Yang, Liu Lei, Huang Yang, Chen Jiehua, Wang Yulei, Liu Zihao, Xin Lingguo, Zhao Yunshan, Wang Wenjian
Shenzhen Children's Hospital, Shenzhen, 518038, China.
Guang'an Men Hospital, China Academy of Chinese Medical Sciences, Beijing, 100095, China.
Stem Cell Res Ther. 2025 Mar 11;16(1):132. doi: 10.1186/s13287-025-04251-3.
Pulmonary fibrosis models play crucial roles in research of pulmonary fibrosis and anti-fibrosis drug screening. Despite the establishment of several pulmonary fibrosis models including lung fibrosis animals, stem cell differentiation, pulmospheres and so on, the one that mimic the personalized native lung lacks.
We here developed a lung organoid-based fibrosis (LOF) model from native lung tissue, and the potential of the LOFs for the sensitivity test of anti-fibrotic drugs was evaluated.
Our results showed that the LOFs could be self-organized from the lung organoids and the fibroblasts derived from native lung tissue. Histochemical examination demonstrated that the LOFs were characteristic of pulmonary fibrosis in structure. Single-cell sequencing (SCS) further revealed that the cell clusters mimicked fibrotic process at cellular and molecular levels in the LOFs. Drug sensitivity test indicated that the LOFs could not only be used to evaluate the efficacy of anti-fibrotic drugs, but also display their toxicity.
We demonstrate that the LOFs represent an efficient fibrotic model that mimics faithfully the personalized characteristics of native lung tissue.
肺纤维化模型在肺纤维化研究和抗纤维化药物筛选中发挥着关键作用。尽管已经建立了多种肺纤维化模型，包括肺纤维化动物模型、干细胞分化模型、肺球模型等，但缺乏能够模拟个性化天然肺的模型。
我们在此从天然肺组织开发了一种基于肺类器官的纤维化（LOF）模型，并评估了LOF在抗纤维化药物敏感性测试中的潜力。
我们的结果表明，LOF可以由肺类器官和源自天然肺组织的成纤维细胞自组织形成。组织化学检查表明，LOF在结构上具有肺纤维化的特征。单细胞测序（SCS）进一步揭示，细胞簇在细胞和分子水平上模拟了LOF中的纤维化过程。药物敏感性测试表明，LOF不仅可用于评估抗纤维化药物的疗效，还可显示其毒性。
我们证明，LOF是一种有效的纤维化模型，能够忠实地模拟天然肺组织的个性化特征。
