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基于肺脱细胞细胞外基质的温敏水凝胶用于三维培养模型以增强癌症干细胞特性。

Thermo-Responsive Hydrogel Based on Lung Decellularized Extracellular Matrix for 3D Culture Model to Enhance Cancer Stem Cell Characteristics.

机构信息

Key Laboratory of Tea Plant Biology of Henan Province, College of Life Sciences, Xinyang Normal University, Xinyang 464000, China.

Library, Xinyang Normal University, Xinyang 464000, China.

出版信息

Molecules. 2024 Sep 15;29(18):4385. doi: 10.3390/molecules29184385.

DOI:10.3390/molecules29184385
PMID:39339380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11433703/
Abstract

Cancer stem cells (CSCs) are most likely the main cause of lung cancer formation, metastasis, drug resistance, and genetic heterogeneity. Three-dimensional (3D) ex vivo cell culture models can facilitate stemness improvement and CSC enrichment. Considering the critical role of extracellular matrix (ECM) on CSC properties, the present study developed a thermo-responsive hydrogel using the porcine decellularized lung for 3D cell culture, and the cell-laden hydrogel culturing model was used to explore the CSC characteristics and potential utilization in CSC-specific drug evaluation. Results showed that the lung dECM hydrogel (LEH) was composed of the main ECM components and displayed excellent cellular compatibility. In addition, lung cancer cells 3D cultured in LEH displayed the overexpression of metastasis-related genes and enhanced migration properties, as compared with those in two-dimensional (2D) conditions. Notably, the CSC features, including the expression level of stemness-associated genes, colony formation capability, drug resistance, and the proportion of cancer stem-like cells (CD133), were also enhanced in 3D cells. Furthermore, the attenuation effect of epigallocatechin gallate (EGCG) on CSC properties in the 3D model was observed, confirming the potential practicability of the 3D culture on CSC-targeted drug screening. Overall, our results suggest that the fabricated LEH is an effective and facile platform for 3D cell culture and CSC-specific drug evaluation.

摘要

癌症干细胞（CSC）很可能是肺癌形成、转移、耐药和遗传异质性的主要原因。三维（3D）体外细胞培养模型可以促进干细胞特性的改善和 CSC 的富集。考虑到细胞外基质（ECM）对 CSC 特性的关键作用，本研究使用猪去细胞化肺构建了一种热响应水凝胶，用于 3D 细胞培养，并用载细胞水凝胶培养模型来探索 CSC 特性和在 CSC 特异性药物评价中的潜在应用。结果表明，肺脱细胞基质水凝胶（LEH）由主要 ECM 成分组成，具有优异的细胞相容性。此外，与二维（2D）条件相比，3D 培养的肺癌细胞中转移相关基因的表达上调，并增强了迁移特性。值得注意的是，与 2D 条件相比，3D 细胞中干细胞相关基因的表达水平、集落形成能力、耐药性和癌症干细胞样细胞（CD133）的比例也增强了 CSC 特性。此外，在 3D 模型中观察到表没食子儿茶素没食子酸酯（EGCG）对 CSC 特性的减弱作用，证实了 3D 培养在 CSC 靶向药物筛选中的潜在实用性。总之，我们的结果表明，所构建的 LEH 是一种用于 3D 细胞培养和 CSC 特异性药物评价的有效且简单的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/dd64a10b6823/molecules-29-04385-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/c857e0292fbd/molecules-29-04385-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/387a08213c7c/molecules-29-04385-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/6150daec91d5/molecules-29-04385-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/df105178f111/molecules-29-04385-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/23714bc81a11/molecules-29-04385-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/a8668ada8eb8/molecules-29-04385-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/5cb37b913e48/molecules-29-04385-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/9a2e09deba62/molecules-29-04385-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/dd64a10b6823/molecules-29-04385-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/c857e0292fbd/molecules-29-04385-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/387a08213c7c/molecules-29-04385-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/6150daec91d5/molecules-29-04385-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/df105178f111/molecules-29-04385-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/23714bc81a11/molecules-29-04385-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/a8668ada8eb8/molecules-29-04385-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/5cb37b913e48/molecules-29-04385-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/9a2e09deba62/molecules-29-04385-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11433703/dd64a10b6823/molecules-29-04385-g008.jpg

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