COVID-19-Prime Time for Microphysiological Systems, as Illustrated for the Brain
COVID-19-Prime Time for Microphysiological Systems, as Illustrated for the Brain
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DOI：
10.14573/altex.2110131
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发表时间：
2021-01-01
影响因子：
5.6
通讯作者：
Hartung, Thomas
中科院分区：
文献类型：
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作者：
Kang, Ian;Smirnova, Lena;Hartung, Thomas
传染病的治疗和预防的发展取决于疾病模型的可用性。人类类器官和芯片上器官的生物工程是一个非常有前途的研究方向。这些微型的实验室培养的器官系统在2019冠状病毒（COVID-19）大流行期间被广泛使用，以显示病原体严重急性呼吸道冠状病毒2（SARS-CoV-2）对人体器官的多种影响。相比之下，大多数动物的接触要么没有导致感染，要么造成轻微的临床症状-而不是许多人遭受的严重感染过程。本文阐明了微生理系统（MPS）在体外研究COVID-19的机会，重点是脑细胞感染及其与COVID-19对人脑影响的翻译相关性。SARS-CoV-2的神经毒力已在10组不同类型的人脑类器官中重现，一致显示一小部分脑细胞的感染伴随有限的病毒复制。这反映了COVID-19患者日益被认可的神经系统表现（病毒感染和脑组织和脑脊液中脑特异性抗体形成的证据）。神经系统症状的发病机制，其长期后果和可能的干预措施仍不清楚，但未来的MPS技术为解决这些悬而未决的问题提供了前景。
The development of therapies for and preventions against infectious diseases depends on the availability of disease models. Bioengineering of human organoids and organs-on-chips is one extremely promising avenue of research. These miniature, laboratory-grown organ systems have been broadly used during the ongoing, unprecedented coronavirus 2019 (COVID-19) pandemic to show the many effects of the etiologic agent, severe acute respiratory coronavirus 2 (SARS-CoV-2) on human organs. In contrast, exposure of most animals either did not result in infection or caused mild clinical signs - not the severe course of the infection suffered by many humans. This article illuminates the opportunities of microphysiological systems (MPS) to study COVID-19 in vitro, with a focus on brain cell infection and its translational relevance to COVID-19 effects on the human brain. Neurovirulence of SARS-CoV-2 has been reproduced in different types of human brain organoids by 10 groups, consistently showing infection of a small portion of brain cells accompanied by limited viral replication. This mirrors increasingly recognized neurological manifestations in COVID-19 patients (evidence of virus infection and brain-specific antibody formation in brain tissue and cerebrospinal fluid). The pathogenesis of neuro-logical signs, their long-term consequences, and possible interventions remain unclear, but future MPS technologies offer prospects to address these open questions.