Defined conditions for long-term expansion of murine and human alveolar epithelial stem cells in three-dimensional cultures

Konishi, Satoshi; Tata, Aleksandra; Tata, Purushothama Rao

doi:10.1016/j.xpro.2022.101447

Cited by 19 publications

(18 citation statements)

References 3 publications

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“…Long-term culturing conditions for organoids derived from airway cells are well established ( Lancaster and Huch, 2019 ; Sachs et al, 2019 ). More recently, conditions for culturing adult alveolar organoids have been published, greatly advancing the lung organoid tool box ( Konishi et al, 2022 ; Katsura et al, 2020 ; Youk et al, 2020 ).…”

Section: Pre-clinical Models For Nsclcmentioning

confidence: 99%

The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures

Balážová

Dost

2023

eLife

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Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Traditional therapeutic approaches such as chemotherapy or radiotherapy have provided only a marginal improvement in the treatment of lung carcinomas. Inhibitors targeting specific genetic aberrations present in non-small cell lung cancer (NSCLC), the most common subtype (85%), have improved the prognostic outlook, but due to the complexity of the LC mutational spectrum, only a fraction of patients benefit from these targeted molecular therapies. More recently, the realization that the immune infiltrate surrounding solid tumors can foster tumor-promoting inflammation has led to the development and implementation of anticancer immunotherapies in the clinic. In NSCLC, one of the most abundant leukocyte infiltrates is macrophages. These highly plastic phagocytes, which are part of the cellular repertoire of the innate immunity, can have a pivotal role in early NSCLC establishment, malignant progression, and tumor invasion. Emerging macrophage-targeting therapies have been focused on the re-differentiation of the macrophages toward an antitumorigenic phenotype, depletion of tumor-promoting macrophage subtypes, or combination therapies combining traditional cytotoxic treatments with immunotherapeutic agents. The most extensively used models employed for the exploration of NSCLC biology and therapy have been 2D cell lines and murine models. However, studying cancer immunology requires appropriately complex models. 3D platforms, including organoid models, are quickly advancing powerful tools to study immune cell-epithelial cell interactions within the tumor microenvironment. Co-cultures of immune cells along with NSCLC organoids allow for an in vitro observation of the tumor microenvironment dynamics closely resembling in vivo settings. Ultimately, the implementation of 3D organoid technology into tumor microenvironment-modeling platforms might facilitate the exploration of macrophage-targeted therapies in NSCLC immunotherapeutic research, thus establishing a new frontier in NSCLC treatment.

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Section: Pre-clinical Models For Nsclcmentioning

confidence: 99%

The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures

Balážová

Dost

2023

eLife

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“…Lungs were inflated with an enzyme dissociation solution (450U/mL Collagenase I (Worthington, LS004197), 5U/mL Dispase (Corning, 354235), and 0.33U/mL DNase I (Roche, 10104159001), in DMEM) ( Katsura et al., 2020 ; Kobayashi et al., 2020 ; Konishi et al., 2022 ). Separated lung lobes were minced and incubated in enzyme solution at 37°C for 25 minutes.…”

Section: Methodsmentioning

confidence: 99%

Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration

Konkimalla¹,

Konishi²,

Kobayashi³

et al. 2022

iScience

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“…For co-culture conditions with alveolar macrophages, naïve DsRed mice were used as the source of AT2 cells (CD31-/CD45-/Ter119-/EpCAM+/Sca1-) while control or injured C57 Bl/6 mice were used as the source of AMs. AM co-cultures used media described in Konishi et al 37 and omitted IL-1β and EGF.…”

Section: Macrophage Depletionmentioning

confidence: 99%

Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages

Wong,

Stark,

et al. 2024

Preprint

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Acute injury in the airways or the lung activates local progenitors and stimulates changes in cell-cell interactions to restore homeostasis, but it is not appreciated how more distant niches are impacted. We utilized mouse models of airway-specific epithelial injury to examine secondary tissue-wide alveolar, immune, and mesenchymal responses. Single-cell transcriptomics and in vivo validation revealed transient, tissue-wide proliferation of alveolar type 2 (AT2) progenitor cells after club cell-specific ablation. The AT2 cell proliferative response was reliant on alveolar macrophages (AMs) via upregulation of Spp1 which encodes the secreted factor Osteopontin. A previously uncharacterized mesenchymal population we termed Mesenchymal Airway/Adventitial Niche Cell 2 (MANC2) also exhibited dynamic changes in abundance and a pro-fibrotic transcriptional signature after club cell ablation in an AM-dependent manner. Overall, these results demonstrate that acute airway damage can trigger distal lung responses including altered cell-cell interactions that may contribute to potential vulnerabilities for further dysregulation and disease.

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Defined conditions for long-term expansion of murine and human alveolar epithelial stem cells in three-dimensional cultures

Cited by 19 publications

References 3 publications

The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures

The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures

Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration

Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages

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