한빛사논문
Yoo-mi Choi7,1, Haram Lee7,2, Minjun Ann3, Minyeong Song2, Jinguen Rheey8,2 and Jinah Jang8,1,3,4,5,6
1Department of Convergence IT Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea
2Gradiant Bioconvergence Inc., Seoul, Republic of Korea
3Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea
4School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Republic of Korea
5Center for 3D Organ Printing and Stem Cells, Pohang University of Science and Technology, Pohang, Republic of Korea
6Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, Republic of Korea
7These authors contributed equally to this work.
8Authors to whom any correspondence should be addressed.
Abstract
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 (LC) model is proposed, which includes patient-derived LC 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 LC microenvironment. In particular, idiopathic pulmonary fibrosis-derived lung fibroblasts 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 LC models that recapitulate lung fibrosis can help determine the appropriate therapy for LC 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 LC patients accompanied by fibrosis.
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