Generation of Human Lung Organoid Cultures from Healthy and Tumor Tissue to Study Infectious Diseases

Salgueiro, Lorena; Kummer, Susann; Sonntag‐Buck, Vera; Weiß, Anne; Schneider, Marc A.; Kräusslich, Hans‐Georg; Sotillo, Rocı́o

doi:10.1128/jvi.00098-22

Cited by 12 publications

(5 citation statements)

References 55 publications

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“…Besides single-cell infections, we found evidence for cell-to-cell transfer of virus proteins, which suggested different mechanisms to be involved in contrast to the infection in 2D cultures. We also observed the formation of infected clusters of cells, which was described very recently for lung organoid cultures as well [ 32 ].…”

Section: Discussionsupporting

confidence: 74%

Human 3D Airway Tissue Models for Real-Time Microscopy: Visualizing Respiratory Virus Spreading

Möckel

Baldok

Walles

et al. 2022

Cells

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Our knowledge about respiratory virus spreading is mostly based on monolayer cultures that hardly reflect the complex organization of the airway epithelium. Thus, there is a strong demand for biologically relevant models. One possibility to study virus spreading at the cellular level is real-time imaging. In an attempt to visualize virus spreading under somewhat more physiological conditions, Calu-3 cells and human primary fibroblasts were co-cultured submerged or as air-liquid interface (ALI). An influenza A virus (IAV) replicating well in cell culture, and carrying a red fluorescent protein (RFP) reporter gene was used for real-time imaging. Our three-dimensional (3D) models exhibited important characteristics of native airway epithelium including a basement membrane, tight junctions and, in ALI models, strong mucus production. In submerged models, first fluorescence signals appeared between 9 and 12 h post infection (hpi) with a low multiplicity of infection of 0.01. Virus spreading further proceeded in the immediate vicinity of infected cells. In ALI models, RFP was found at 22 hpi and later. Consequently, the progression of infection was delayed, in contrast to the submerged model. With these features, we believe that our 3D airway models can deliver new insights in the spreading of IAV and other respiratory viruses.

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Section: Discussionsupporting

confidence: 74%

Human 3D Airway Tissue Models for Real-Time Microscopy: Visualizing Respiratory Virus Spreading

Möckel

Baldok

Walles

et al. 2022

Cells

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“…Another study showed that the influenza B virus preferably infects the upper respiratory tract over the lower lung while suggesting that it has a replicative rate and tropism similar to influenza A [47]. Additionally, the usage of lung organoids also revealed that the replication of influenza A virus tends to form a specific foci, and is not randomly dispersed as shown by previous monoclonal cultures [94]. During infection of the lung organoid, IFN-related genes and proinflammatory genes were activated to mediate an immune response [94].…”

Section: Respiratory Organoidmentioning

confidence: 85%

“…Additionally, the usage of lung organoids also revealed that the replication of influenza A virus tends to form a specific foci, and is not randomly dispersed as shown by previous monoclonal cultures [94]. During infection of the lung organoid, IFN-related genes and proinflammatory genes were activated to mediate an immune response [94]. In addition, the infectivity of different influenza strains has been assessed using a human airway organoid [48].…”

Section: Respiratory Organoidmentioning

confidence: 86%

3D Human Organoids: The Next “Viral” Model for the Molecular Basis of Infectious Diseases

2022

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The COVID-19 pandemic has driven the scientific community to adopt an efficient and reliable model that could keep up with the infectious disease arms race. Coinciding with the pandemic, three dimensional (3D) human organoids technology has also gained traction in the field of infectious disease. An in vitro construct that can closely resemble the in vivo organ, organoid technology could bridge the gap between the traditional two-dimensional (2D) cell culture and animal models. By harnessing the multi-lineage characteristic of the organoid that allows for the recapitulation of the organotypic structure and functions, 3D human organoids have emerged as an essential tool in the field of infectious disease research. In this review, we will be providing a comparison between conventional systems and organoid models. We will also be highlighting how organoids played a role in modelling common infectious diseases and molecular mechanisms behind the pathogenesis of causative agents. Additionally, we present the limitations associated with the current organoid models and innovative strategies that could resolve these shortcomings.

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“…For infections, 3D organoids provide a means to characterize pathogens and determine the response to infection. They demonstrated that lung organoids that were derived from cancer cells show greater susceptibility to infection by the influenza A virus with a reduced innate immune response compared to organoids from healthy tissue (66,67).…”

Section: Infectious Diseasementioning

confidence: 99%

Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

Kim

Lee

Seo

2023

BMB Rep

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Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal.Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo.However, the information provided by an MCTS model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases. clinical utility of drugs that proved effective in vitro is low. Also, assays of liver function, including cell polarization, albumin synthesis, bile secretion, and urea synthesis, are better when they are performed in three-dimensional (3D) cell cultures that more accurately reflect the normal context of liver cells (7). Similarly, 3D cells provide a better model system for cancer drug discovery.The interactions between the tumor and the tumor microenvironment (TME) play a critical role in cell differentiation, tumorigenesis, metastasis, and the efficacy of drug therapies. Therefore it was important to develop a 3D TME platform to discover new therapeutics for liver cancer drug discovery. These platforms are complex and expensive to produce; however, the recently developed multicellular tumor spheroid (MCTS) models provide a new platform for highthroughput screening (HTS) of drugs to treat a variety of diseases, including cancers and infections.The development of 3D multicellular hepatic spheroid (MCHS) models has had a major impact on drug discovery and the identification of novel targets for the treatment of HCC and fibrosis. MCHS models should greatly increase the number of potential new drugs to treat HCC and reduce the time to drug discovery.In this review, we describe the influence of components of the TME on tumorigenesis, fibrogenesis, and chemoresistance in HCC, as well as advanced strategies that exploit 3D multicellular spheroid models to identify novel cancer targets and therapeutics.

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Generation of Human Lung Organoid Cultures from Healthy and Tumor Tissue to Study Infectious Diseases

Cited by 12 publications

References 55 publications

Human 3D Airway Tissue Models for Real-Time Microscopy: Visualizing Respiratory Virus Spreading

Human 3D Airway Tissue Models for Real-Time Microscopy: Visualizing Respiratory Virus Spreading

3D Human Organoids: The Next “Viral” Model for the Molecular Basis of Infectious Diseases

Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

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