Monteiro Cátia F, Santos Sara C, Custódio Catarina A, Mano João F
Department of Chemistry CICECO University of Aveiro Campus Universitário de Santiago 3810-193 Aveiro Portugal.
Adv Sci (Weinh). 2020 Feb 11;7(7):1902398. doi: 10.1002/advs.201902398. eCollection 2020 Apr.
Fundamental physiologic and pathologic phenomena such as wound healing and cancer metastasis are typically associated with the migration of cells through adjacent extracellular matrix. In recent years, advances in biomimetic materials have supported the progress in 3D cell culture and provided biomedical tools for the development of models to study spheroid invasiveness. Despite this, the exceptional biochemical and biomechanical properties of human-derived materials are poorly explored. Human methacryloyl platelet lysates (PLMA)-based hydrogels are herein proposed as reliable 3D platforms to sustain in vivo-like cell invasion mechanisms. A systematic analysis of spheroid viability, size, and invasiveness is performed in three biomimetic materials: PLMA hydrogels at three different concentrations, poly(ethylene glycol) diacrylate, and Matrigel. Results demonstrate that PLMA hydrogels perfectly support the recapitulation of the tumor invasion behavior of cancer cell lines (MG-63, SaOS-2, and A549) and human bone-marrow mesenchymal stem cell spheroids. The distinct invasiveness ability of each cell type is reflected in the PLMA hydrogels and, furthermore, different mechanical properties produce an altered invasive behavior. The herein presented human PLMA-based hydrogels could represent an opportunity to develop accurate cell invasiveness models and open up new possibilities for humanized and personalized high-throughput screening and validation of anticancer drugs.
诸如伤口愈合和癌症转移等基本生理和病理现象通常与细胞通过相邻细胞外基质的迁移有关。近年来，仿生材料的进展推动了三维细胞培养的发展，并为研究球体侵袭性的模型开发提供了生物医学工具。尽管如此，人类来源材料卓越的生化和生物力学特性仍未得到充分探索。本文提出基于人类甲基丙烯酰化血小板裂解物（PLMA）的水凝胶作为可靠的三维平台，以维持类似体内的细胞侵袭机制。在三种仿生材料中对球体活力、大小和侵袭性进行了系统分析：三种不同浓度的PLMA水凝胶、聚乙二醇二丙烯酸酯和基质胶。结果表明，PLMA水凝胶能够完美地支持癌细胞系（MG-63、SaOS-2和A549）和人类骨髓间充质干细胞球体肿瘤侵袭行为的重现。每种细胞类型独特的侵袭能力在PLMA水凝胶中得到体现，此外，不同的力学性能会产生改变的侵袭行为。本文介绍的基于人类PLMA的水凝胶可能为开发精确的细胞侵袭模型提供契机，并为抗癌药物的人源化和个性化高通量筛选及验证开辟新的可能性。
