Human microvasculature-on-a chip: anti-neovasculogenic effect of nintedanib in vitro

Zeinali, Soheila; Bichsel, Colette A.; Hobi, Nina; Funke, Manuela; Marti, Thomas M.; Schmid, Ralph A.; Guenat, Olivier T.; Geiser, Thomas (2018). Human microvasculature-on-a chip: anti-neovasculogenic effect of nintedanib in vitro. Angiogenesis, 21(4), pp. 861-871. Springer Netherlands 10.1007/s10456-018-9631-8

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Idiopathic pulmonary fibrosis is characterized by a progressive scarring and stiffening of the peripheral lung tissue that decreases lung function. Over the course of the disease, the lung microvasculature undergoes extensive remodeling. There is increased angiogenesis around fibrotic foci and an absence of microvessels within the foci. To elucidate how the anti-fibrotic drug nintedanib acts on vascular remodeling, we used an in vitro model of perfusable microvessels made with primary endothelial cells and primary lung fibroblasts in a microfluidic chip. The microvasculature model allowed us to study the impact of nintedanib on permeability, vascularized area, and cell-cell interactions. The anti-vasculogenic impact of nintedanib was visible at the minimal concentrations of 10 nM, showing a significant increase in vessel permeability. Furthermore, nintedanib decreased microvessel density, diameter, and influenced fibroblast organization around endothelial microvessels. These results show that nintedanib acts on the endothelial network formation and endothelial-perivascular interactions. Advanced in vitro microvasculature models may thus serve to pinpoint the mechanistic effect of anti-fibrotic drugs on the microvascular remodeling in 3D and refine findings from animal studies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research > ARTORG Center - Lung Regeneration Technologies
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Zeinali, Soheila; Bichsel, Colette; Hobi, Nina; Funke-Chambour, Manuela; Marti, Thomas; Schmid, Ralph; Guenat, Olivier Thierry and Geiser, Thomas

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 620 Engineering

ISSN:

0969-6970

Publisher:

Springer Netherlands

Language:

English

Submitter:

Olivier Thierry Guenat

Date Deposited:

22 Aug 2018 16:03

Last Modified:

18 Jan 2019 16:11

Publisher DOI:

10.1007/s10456-018-9631-8

PubMed ID:

29967964

BORIS DOI:

10.7892/boris.119457

URI:

https://boris.unibe.ch/id/eprint/119457

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