A Human 3D neural assembloid model for SARS-CoV-2 infection

Gleeson, Joseph G.; Wang, Lu; Sievert, David; Clark, Alex E.; Federman, Hannah; Gastfriend, Benjamin D.; Shusta, Eric V.; Palecek, Sean P.; Carlin, Aaron F.

doi:10.21203/rs.3.rs-214352/v1

Cited by 4 publications

(5 citation statements)

References 39 publications

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“…They found that SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) gene copies in the supernatant increased over time, suggesting that the infected cells could release viral particles ( Zhang and others 2020 ). Similarly, Song and others (2020) , Tiwari and others (2021) , and Gleeson and others (2021) showed evidence of SARS-CoV-2 replication in a brain organoid. Furthermore, viral particles and regions of budding from endoplasmic reticulum-like structures were observed in the organoids using electron microscopy, suggesting that SARS-CoV-2 could even replicate within neurons ( Song and others 2020 ).…”

Section: Sars-cov-2 Neurotropismmentioning

confidence: 84%

“…It has been shown that cerebral organoids are able to form complex brain architectures spontaneously using intrinsic signals ( Benito-Kwiecinski and Lancaster 2020 ). The remaining five studies employed a variety of patterning factors and media that promoted regional specificity of brain organoids like the forebrain, midbrain, hippocampus and hypothalamus organoids ( Gleeson and others 2021 ; Jacob and others 2020 ; Ramani and others 2020 ; Yi and others 2020 ; Zhang and others 2020 ). Particularly, the generation of choroid plexus containing organoids was interesting given that there were two recent studies that highlighted significant susceptibility of the choroid plexus organoid (CPO) to SARS-CoV-2 ( Jacob and others 2020 ; Pellegrini and others 2020 ).…”

Section: Sars-cov-2 Neurotropismmentioning

confidence: 99%

“…2 ) include the development of high throughput evaluation to analyze the transcriptomes, epigenetics, and proteomics of infected brain organoids and the use of patient-derived organoids for different stages of COVID-19 infection and recovery to draw correlation between pathophysiology and neuropsychiatric clinical findings. Gleeson and others (2021) integrated perivascular cells into cortical organoids and found that cortical organoids with the pericyte-like cells had more extensive SARS-CoV-2 infection than the traditional cortical organoids. It would be interesting to evaluate SARS-CoV-2 infection in choroid plexus organoids with perivascular cells.…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

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Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids

Sun

et al. 2021

Neuroscientist

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Neuropsychiatric manifestations of coronavirus disease 2019 (COVID-19) have been increasingly recognized. However, the pathophysiology of COVID-19 in the central nervous system remains unclear. Brain organoid models derived from human pluripotent stem cells are potentially useful for the study of complex physiological and pathological processes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as they recapitulate cellular heterogeneity and function of individual tissues. We identified brain organoid studies that provided insight into the neurotropic properties of SARS-CoV-2. While SARS-CoV-2 was able to infect neurons, the extent of neurotropism was relatively limited. Conversely, choroidal epithelial cells consistently showed a high susceptibility to SARS-CoV-2 infection. Brain organoid studies also elucidated potential mechanism for cellular entry, demonstrated viral replication, and highlighted downstream cellular effects of SARS-CoV-2 infection. Collectively, they suggest that the neuropsychiatric manifestations of COVID-19 may be contributed by both direct neuronal invasion and indirect consequences of neuroinflammation. The use of high throughput evaluation, patient-derived organoids, and advent of “assembloids” will provide a better understanding and functional characterization of the neuropsychiatric symptoms seen in post-acute COVID-19 syndrome. With advancement of organoid technology, brain organoids offer a promising tool for unravelling pathophysiologic clues and potential therapeutic options for neuropsychiatric complications of COVID-19.

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Section: Sars-cov-2 Neurotropismmentioning

confidence: 84%

Section: Sars-cov-2 Neurotropismmentioning

confidence: 99%

Section: Challenges and Future Directionsmentioning

confidence: 99%

See 1 more Smart Citation

Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids

Sun

et al. 2021

Neuroscientist

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“…Accordingly, the combination of microglia-like cells and cortical organoids was previously used to model certain aspects of Alzheimer’s disease [ 144 ]. Furthermore, the introduction of pericyte-like cells enabled the successful infection of cortical organoids with SARS-CoV-2 [ 145 ]. The introduction of immune cells to organoids is especially highly desired in logical and immunological research.…”

Section: Complex In Vitro Models In Viral Researchmentioning

confidence: 99%

Animal Model Alternatives in Filovirus and Bornavirus Research

Widerspick

Steffen

Tappe

et al. 2023

Viruses

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The order Mononegavirales contains a variety of highly pathogenic viruses that may infect humans, including the families Filoviridae, Bornaviridae, Paramyxoviridae, and Rhabodoviridae. Animal models have historically been important to study virus pathogenicity and to develop medical countermeasures. As these have inherent shortcomings, the rise of microphysiological systems and organoids able to recapitulate hallmarks of the diseases caused by these viruses may have enormous potential to add to or partially replace animal modeling in the future. Indeed, microphysiological systems and organoids are already used in the pharmaceutical R&D pipeline because they are prefigured to overcome the translational gap between model systems and clinical studies. Moreover, they may serve to alleviate ethical concerns related to animal research. In this review, we discuss the value of animal model alternatives in human pathogenic filovirus and bornavirus research. The current animal models and their limitations are presented followed by an overview of existing alternatives, such as organoids and microphysiological systems, which might help answering open research questions.

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“…In addition, researches demonstrated that ACE2 is also expressed in pericytes, another apart of mural cells of the central nervous system (CNS). SARS-CoV-2 may directly destroy pericyte and further reduce blood supply to the brain, and ultimately result in neuronal dysfunction [90,91]. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points [92].…”

Section: Covid-19 On Nervous Systemmentioning

confidence: 99%

COVID-19: systemic pathology and its implications for therapy

Shen¹,

Li²,

Zhang³

et al. 2022

Int. J. Biol. Sci.

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Responding to the coronavirus disease 2019 (COVID-19) pandemic has been an unexpected and unprecedented global challenge for humanity in this century. During this crisis, specialists from the laboratories and frontline clinical personnel have made great efforts to prevent and treat COVID-19 by revealing the molecular biological characteristics and epidemic characteristics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, SARS-CoV-2 has severe consequences for public health, including human respiratory system, immune system, blood circulation system, nervous system, motor system, urinary system, reproductive system and digestive system. In the review, we summarize the physiological and pathological damage of SARS-CoV-2 to these systems and its molecular mechanisms followed by clinical manifestation. Concurrently, the prevention and treatment strategies of COVID-19 will be discussed in preclinical and clinical studies. With constantly unfolding and expanding scientific understanding about COVID-19, the updated information can help applied researchers understand the disease to build potential antiviral drugs or vaccines, and formulate creative therapeutic ideas for combating COVID-19 at speed.

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A Human 3D neural assembloid model for SARS-CoV-2 infection

Cited by 4 publications

References 39 publications

Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids

Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids

Animal Model Alternatives in Filovirus and Bornavirus Research

COVID-19: systemic pathology and its implications for therapy

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