基于细胞外基质的肝脏脱细胞三维肿瘤构建体,提高药物筛选效率。

IF 5.6 1区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Regenerative Biomaterials Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI:10.1093/rb/rbae113
Shengchang Luo, Qingqing Wang, Miaoting Li, Peiyao Xu, Yicheng Wang, Ying Wang, Ranjith Kumar Kankala, Shibin Wang, Aizheng Chen
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引用次数: 0

摘要

脱细胞细胞外基质(decellularized extracellular matrix,dECM)已成为复制肿瘤微环境(TME)活体相似条件的有效介质,从而提高了化疗药物筛选的准确性。然而,最近基于 dECM 的肿瘤模型出现了形态不可控和细胞活力减弱等挑战,阻碍了化疗疗效的精确评估。在这里,我们利用一种定制的微流体方法,将猪肝中的dECM包裹在高度聚乳酸-聚乙二醇酸(PLGA)多孔微球(dECM-PLGA PMs)中,从而设计出一种三维(3D)肿瘤模型。由于细胞外基质(ECM)微纤维和生物分子成分注入到微球中,这些基于dECM-PLGA微球的微肿瘤与单独的PLGA微球相比,能显著促进肝癌细胞(HepG2)的增殖。对 dECM 的蛋白质组分析进一步揭示了嵌入 PMs 中的这些生物活性片段的潜在作用。值得注意的是,基于 dECM-PLGA PMs 的微组织有效地复制了肿瘤的耐药性特征,在半数最大抑制浓度 (IC50) 值上显示出明显的差异,这可能与 TME 的某些方面相对应。总之,这些 dECM-PLGA PMs 大大克服了传统三维肿瘤模型中微观结构不规则和细胞存活率不理想的普遍挑战。它们还为药物测试提供了一个可持续、可扩展的平台,为未来的药物评估带来了希望。
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Engineered liver-derived decellularized extracellular matrix-based three-dimensional tumor constructs for enhanced drug screening efficiency.

The decellularized extracellular matrix (dECM) has emerged as an effective medium for replicating the in vivo-like conditions of the tumor microenvironment (TME), thus enhancing the screening accuracy of chemotherapeutic agents. However, recent dECM-based tumor models have exhibited challenges such as uncontrollable morphology and diminished cell viability, hindering the precise evaluation of chemotherapeutic efficacy. Herein, we utilized a tailor-made microfluidic approach to encapsulate dECM from porcine liver in highly poly(lactic-co-glycolic acid) (PLGA) porous microspheres (dECM-PLGA PMs) to engineer a three-dimensional (3D) tumor model. These dECM-PLGA PMs-based microtumors exhibited significant promotion of hepatoma carcinoma cells (HepG2) proliferation compared to PLGA PMs alone, since the infusion of extracellular matrix (ECM) microfibers and biomolecular constituents within the PMs. Proteomic analysis of the dECM further revealed the potential effects of these bioactive fragments embedded in the PMs. Notably, dECM-PLGA PMs-based microtissues effectively replicated the drug resistance traits of tumors, showing pronounced disparities in half-maximal inhibitory concentration (IC50) values, which could correspond with certain aspects of the TME. Collectively, these dECM-PLGA PMs substantially surmounted the prevalent challenges of unregulated microstructure and suboptimal cell viability in conventional 3D tumor models. They also offer a sustainable and scalable platform for drug testing, holding promise for future pharmaceutical evaluations.

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来源期刊
Regenerative Biomaterials
Regenerative Biomaterials Materials Science-Biomaterials
CiteScore
7.90
自引率
16.40%
发文量
92
审稿时长
10 weeks
期刊介绍: Regenerative Biomaterials is an international, interdisciplinary, peer-reviewed journal publishing the latest advances in biomaterials and regenerative medicine. The journal provides a forum for the publication of original research papers, reviews, clinical case reports, and commentaries on the topics relevant to the development of advanced regenerative biomaterials concerning novel regenerative technologies and therapeutic approaches for the regeneration and repair of damaged tissues and organs. The interactions of biomaterials with cells and tissue, especially with stem cells, will be of particular focus.
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