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Next generation organoids for biomedical research and applications
Biotechnology Advances ( IF 16.0 ) Pub Date : 2017-10-19 , DOI: 10.1016/j.biotechadv.2017.10.005
Yan-Ru Lou , Alan W. Leung

Organoids are in vitro cultures of miniature fetal or adult organ-like structures. Their potentials for use in tissue and organ replacement, disease modeling, toxicology studies, and drug discovery are tremendous. Currently, major challenges facing human organoid technology include (i) improving the range of cellular heterogeneity for a particular organoid system, (ii) mimicking the native micro- and matrix-environment encountered by cells within organoids, and (iii) developing robust protocols for the in vitro maturation of organoids that remain mostly fetal-like in cultures. To tackle these challenges, we advocate the principle of reverse engineering that replicates the inner workings of in vivo systems with the goal of achieving functionality and maturation of the resulting organoid structures with the input of minimal intrinsic (cellular) and environmental (matrix and niche) constituents. Here, we present an overview of organoid technology development in several systems that employ cell materials derived from fetal and adult tissues and pluripotent stem cell cultures. We focus on key studies that exploit the self-organizing property of embryonic progenitors and the role of designer matrices and cell-free scaffolds in assisting organoid formation. We further explore the relationship between adult stem cells, niche factors, and other current developments that aim to enhance robust organoid maturation. From these works, we propose a standardized pipeline for the development of future protocols that would help generate more physiologically relevant human organoids for various biomedical applications.



中文翻译:

用于生物医学研究和应用的下一代类器官

类器官是微型胎儿或成年器官样结构的体外培养物。它们在组织和器官置换,疾病建模,毒理学研究和药物发现中的应用潜力巨大。当前,人类类器官技术面临的主要挑战包括:(i)改善特定类器官系统的细胞异质性范围;(ii)模仿类器官内细胞所遇到的天然微环境和基质环境;以及(iii)为以下方面开发可靠的协议类器官的体外成熟,在培养物中大多数仍为类胎儿。为了应对这些挑战,我们提倡逆向工程原理,该原理可以复制体内的内部原理这些系统的目标是通过输入最少的固有(细胞)和环境(矩阵和小生境)成分来实现所得类器官结构的功能性和成熟度。在这里,我们概述了类器官系统技术的发展概况,这些系统采用了来自胎儿和成人组织以及多能干细胞培养物的细胞材料。我们专注于利用胚胎祖细胞的自组织特性以及设计基质和无细胞支架在协助类器官形成中的作用的关键研究。我们进一步探讨成人干细胞,利基因子和其他旨在增强鲁棒类器官成熟度的当前发展之间的关系。从这些作品中

更新日期:2017-10-19
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