3D bioprinted vascularized lung cancer organoid models with underlying disease capable of more precise drug evaluation
| Autor: | Yoo-mi Choi, Haram Lee, Minjun Ahn, Minyeong Song, Jinguen Rheey, Jinah Jang |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Biofabrication. |
| ISSN: | 1758-5090 1758-5082 |
| Popis: | Despite encouraging progress in the development of in vitro cancer models, in vitro cancer models that simultaneously recapitulate the complexity of the tumor microenvironment and its diverse cellular components and genetic properties remain lacking. Here, an advanced vascularized lung cancer model is proposed, which includes patient-derived lung cancer organoids (LCOs), lung fibroblasts, and perfusable vessels using 3D bioprinting technology. To better recapitulate the biochemical composition of native lung tissues, a porcine lung-derived decellularized extracellular matrix (LudECM) hydrogel was produced to offer physical and biochemical cues to cells in the lung cancer microenvironment. In particular, idiopathic pulmonary fibrosis-derived lung fibroblasts (iLFs) were used to implement fibrotic niches similar to actual human fibrosis. It was shown that they increased cell proliferation and the expression of drug resistance-related genes in LCOs with fibrosis. In addition, changes in resistance to sensitizing targeted anti-cancer drugs in LCOs with fibrosis were significantly greater in LudECM than in that Matrigel. Therefore, assessment of drug responsiveness in vascularized lung cancer models that recapitulate lung fibrosis can help determine the appropriate therapy for lung cancer patients accompanied by fibrosis. Furthermore, it is expected that this approach could be utilized for the development of targeted therapies or the identification of biomarkers for lung cancer patients accompanied by fibrosis. |
| Databáze: | OpenAIRE |
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