In Vitro Three-dimensional (3D) Cell Culture Tools for Spheroid and Organoid Models

Sang-Yun Lee, In-Seong Koo, Hyun Ju Hwang, Dong Woo Lee
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Abstract

Three-dimensional (3D) cell culture technology has been steadily studied since the 1990’s due to its superior biocompatibility compared to the conventional two-dimensional (2D) cell culture technology, and has recently developed into an organoid culture technology that further improved biocompatibility. Since the 3D culture of human cell lines in artificial scaffolds was demonstrated in the early 90′s, 3D cell culture technology has been actively developed owing to various needs in the areas of disease research, precision medicine, new drug development, and some of these technologies have been commercialized. In particular, 3D cell culture technology is actively being applied and utilized in drug development and cancer-related precision medicine research. Drug development is a long and expensive process that involves multiple steps—from target identification to lead discovery and optimization, preclinical studies, and clinical trials for approval for clinical use. Cancer ranks first among life-threatening diseases owing to intra-tumoral heterogeneity associated with metastasis, recurrence, and treatment resistance, ultimately contributing to treatment failure and adverse prognoses. Therefore, there is an urgent need for the development of efficient drugs using 3D cell culture techniques that can closely mimic in vivo cellular environments and customized tumor models that faithfully represent the tumor heterogeneity of individual patients. This review discusses 3D cell culture technology focusing on research trends, commercialization status, and expected effects developed until recently. We aim to summarize the great potential of 3D cell culture technology and contribute to expanding the base of this technology.

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用于球形和类器官模型的体外三维(3D)细胞培养工具
三维(3D)细胞培养技术与传统的二维(2D)细胞培养技术相比,具有更优越的生物相容性,因此自 20 世纪 90 年代以来,三维(3D)细胞培养技术的研究一直在稳步进行,最近又发展成为进一步提高生物相容性的类器官培养技术。自上世纪 90 年代初人类细胞系在人工支架中进行三维培养得到证实以来,三维细胞培养技术因疾病研究、精准医疗、新药开发等领域的各种需求而得到了积极发展,其中一些技术已实现商业化。其中,三维细胞培养技术在药物开发和癌症相关的精准医学研究中得到了积极的应用和利用。药物开发是一个漫长而昂贵的过程,涉及多个步骤--从靶点识别到先导物的发现和优化、临床前研究以及批准临床使用的临床试验。在威胁生命的疾病中,癌症居首位,这是因为肿瘤内异质性与转移、复发和耐药性有关,最终导致治疗失败和不良预后。因此,利用三维细胞培养技术开发高效药物迫在眉睫,这种技术可以密切模拟体内细胞环境和定制肿瘤模型,忠实再现个体患者的肿瘤异质性。本综述将重点讨论三维细胞培养技术的研究趋势、商业化现状以及近期开发的预期效果。我们旨在总结三维细胞培养技术的巨大潜力,并为扩大该技术的基础做出贡献。
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