Dataset Information

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast-Keratinocyte Interaction in a 3D Co-Culture Model.

ABSTRACT: Microgravity impairs tissue organization and critical pathways involved in the cell-microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization.

SUBMITTER: Fedeli V

PROVIDER: S-EPMC8879576 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast-Keratinocyte Interaction in a 3D Co-Culture Model.

Fedeli Valeria V Cucina Alessandra A Dinicola Simona S Fabrizi Gianmarco G Catizone Angela A Gesualdi Luisa L Ceccarelli Simona S Harrath Abdel Halim AH Alwasel Saleh H SH Ricci Giulia G Pedata Paola P Bizzarri Mariano M Monti Noemi N

International journal of molecular sciences 20220216 4

Microgravity impairs tissue organization and critical pathways involved in the cell-microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and ...[more]

PMID: 35216279

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Project description:Colorectal cancer (CRC) remains one of the most aggressive and lethal cancers, with metastasis accounting for most deaths. As such, there is an unmet need for improved therapies for metastatic CRC (mCRC). Currently, the research focus is shifting towards the reciprocal interactions within the tumor microenvironment (TME), which prevent tumor clearance by the immune system. Dendritic cells (DCs) play a key role in the initiation and amplification of anti-tumor immune responses and in driving the clinical success of immunotherapies. Dissecting the interactions between DCs and CRC cells may open doors to identifying key mediators in tumor progression, and possible therapeutic targets. This requires representative, robust and versatile models and tools. Currently, there is a shortage of such in vitro systems to model the CRC TME and its tumor-immune cell interactions. Here we develop and establish a dynamic organotypic 3D co-culture system to recapitulate and untangle the interactions between DCs and patient-derived mCRC tumor organoids. To our knowledge, this is the first study investigating human DCs in co-culture with tumor organoids in a 3D, organotypic setting. This system reveals how mCRC organoids modulate and shape monocyte-derived DCs (MoDCs) behavior, phenotype, and function, within a collagen matrix, using techniques such as brightfield and fluorescence microscopy, flow cytometry, and fluorescence-activated cell sorting. Our 3D co-culture model shows high viability and extensive interaction between DCs and tumor organoids, and its structure resembles patient tissue sections. Furthermore, it is possible to retrieve DCs from the co-cultures and characterize their phenotypic and functional profile. In our study, the expression of activation markers in both mature and immature DCs and their ability to activate T cells were impacted by co-culture with tumor organoids. In the future, this direct co-culture platform can be adapted and exploited to study the CRC-DC interplay in more detail, enabling novel and broader insights into CRC-driven DC (dys)function.

Dataset Information

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast-Keratinocyte Interaction in a 3D Co-Culture Model.

Publications

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast-Keratinocyte Interaction in a 3D Co-Culture Model.

Similar Datasets

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