Abstract：
Organoids are small, self-organizing three-dimensional cell cultures that are derived from stem cells or primary organs. These cultures replicate the complexity of an organ, which cannot be achieved by single-cell culture systems. Organoids can be used in testing of new drugs instead of animals. Development and validation of organoids is thus important to reduce the reliance on animals for drug testing. In this review, we have discussed the developmental and regulatory aspects of organoids and highlighted their importance in drug development. We have first summarized different types of culture-based organoid systems such as submerged Matrigel, micro-fluidic 3D cultures, inducible pluripotent stem cells, and air-liquid interface cultures. These systems help us understand the intricate interplay between cells and their surrounding milieu for identifying functions of target receptors, soluble factors, and spatial interactions. Further, we have discussed the advances in humanized severe-combined immunodeficiency mouse models and their applications in the pharmacology of immune-oncology. Since regulatory aspects are important in using organoids for drug development, we have summarized FDA and EMA regulations on organoid research to support pre-clinical studies. Finally, we have included some unique studies highlighting the use of organoids in studying infectious diseases, cancer, and fundamental biology. These studies also exemplify the latest technological advances in organoid development resulting in improved efficiency. Overall, this review comprehensively summarizes the applications of organoids in early drug development during discovery and pre-clinical studies.
摘要：
类器官很小，来自干细胞或初级器官的自组织三维细胞培养物。这些文化复制了器官的复杂性，这是单细胞培养系统无法实现的。类器官可用于测试新药而不是动物。因此，类器官的开发和验证对于减少药物测试对动物的依赖非常重要。在这次审查中,我们已经讨论了类器官的发展和监管方面，并强调了它们在药物开发中的重要性。我们首先总结了不同类型的基于培养的类器官系统，例如浸没的Matrigel，微流体3D培养，可诱导多能干细胞，和气-液界面培养物。这些系统帮助我们了解细胞及其周围环境之间复杂的相互作用，以识别目标受体的功能，可溶性因子，和空间相互作用。Further,我们讨论了人源化严重联合免疫缺陷小鼠模型的进展及其在免疫肿瘤学药理学中的应用.由于监管方面在使用类器官进行药物开发中很重要，我们总结了FDA和EMA关于类器官研究的规定,以支持临床前研究.最后,我们纳入了一些独特的研究，强调类器官在传染病研究中的应用，癌症,和基础生物学。这些研究还举例说明了类器官开发的最新技术进步，从而提高了效率。总的来说,这篇综述全面总结了类器官在发现和临床前研究中早期药物开发中的应用。
