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诱导多能干细胞衍生类器官:它们在新冠病毒疾病建模中的意义

Induced Pluripotent Stem Cell-Derived Organoids: Their Implication in COVID-19 Modeling.

作者信息

Csöbönyeiová Mária, Klein Martin, Kuniaková Marcela, Varga Ivan, Danišovič Ľuboš

机构信息

Regenmed Ltd., Medena 29, 811 01 Bratislava, Slovakia.

Institute of Histology and Embryology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.

出版信息

Int J Mol Sci. 2023 Feb 9;24(4):3459. doi: 10.3390/ijms24043459.

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant global health issue. This novel virus's high morbidity and mortality rates have prompted the scientific community to quickly find the best COVID-19 model to investigate all pathological processes underlining its activity and, more importantly, search for optimal drug therapy with minimal toxicity risk. The gold standard in disease modeling involves animal and monolayer culture models; however, these models do not fully reflect the response to human tissues affected by the virus. However, more physiological 3D in vitro culture models, such as spheroids and organoids derived from induced pluripotent stem cells (iPSCs), could serve as promising alternatives. Different iPSC-derived organoids, such as lung, cardiac, brain, intestinal, kidney, liver, nasal, retinal, skin, and pancreatic organoids, have already shown immense potential in COVID-19 modeling. In the present comprehensive review article, we summarize the current knowledge on COVID-19 modeling and drug screening using selected iPSC-derived 3D culture models, including lung, brain, intestinal, cardiac, blood vessels, liver, kidney, and inner ear organoids. Undoubtedly, according to reviewed studies, organoids are the state-of-the-art approach to COVID-19 modeling.

摘要

由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)疫情已成为一个重大的全球健康问题。这种新型病毒的高发病率和死亡率促使科学界迅速找到最佳的COVID-19模型,以研究其活动背后的所有病理过程,更重要的是,寻找毒性风险最小的最佳药物治疗方法。疾病建模的金标准包括动物模型和单层培养模型;然而,这些模型不能完全反映受病毒影响的人体组织的反应。然而,更具生理学意义的三维体外培养模型,如源自诱导多能干细胞(iPSC)的球体和类器官,可能是很有前景的替代方案。不同的iPSC来源的类器官,如肺、心脏、脑、肠、肾、肝、鼻、视网膜、皮肤和胰腺类器官,在COVID-19建模中已经显示出巨大的潜力。在本篇全面的综述文章中,我们总结了目前使用选定的iPSC来源的三维培养模型(包括肺、脑、肠、心脏、血管、肝、肾和内耳类器官)进行COVID-19建模和药物筛选的相关知识。毫无疑问,根据已审查的研究,类器官是COVID-19建模的前沿方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d2c/9961667/17736b41159c/ijms-24-03459-g001.jpg

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