Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip

Summary: The endothelium of blood vessels is a vital organ that reacts differently to subtle changes in stiffness and mechanical forces exerted on its environment (extracellular matrix (ECM)). Upon alteration of these biomechanical cues, endothelial cells initiate signaling pathways that govern vasc...

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Main Authors: Dario Ferrari, Arunima Sengupta, Lyong Heo, Laszlo Pethö, Johann Michler, Thomas Geiser, Vinicio A. de Jesus Perez, Wolfgang M. Kuebler, Soheila Zeinali, Olivier T. Guenat
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223002754
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author Dario Ferrari
Arunima Sengupta
Lyong Heo
Laszlo Pethö
Johann Michler
Thomas Geiser
Vinicio A. de Jesus Perez
Wolfgang M. Kuebler
Soheila Zeinali
Olivier T. Guenat
author_facet Dario Ferrari
Arunima Sengupta
Lyong Heo
Laszlo Pethö
Johann Michler
Thomas Geiser
Vinicio A. de Jesus Perez
Wolfgang M. Kuebler
Soheila Zeinali
Olivier T. Guenat
author_sort Dario Ferrari
collection DOAJ
description Summary: The endothelium of blood vessels is a vital organ that reacts differently to subtle changes in stiffness and mechanical forces exerted on its environment (extracellular matrix (ECM)). Upon alteration of these biomechanical cues, endothelial cells initiate signaling pathways that govern vascular remodeling. The emerging organs-on-chip technologies allow the mimicking of complex microvasculature networks, identifying the combined or singular effects of these biomechanical or biochemical stimuli. Here, we present a microvasculature-on-chip model to investigate the singular effect of ECM stiffness and mechanical cyclic stretch on vascular development. Following two different approaches for vascular growth, the effect of ECM stiffness on sprouting angiogenesis and the effect of cyclic stretch on endothelial vasculogenesis are studied. Our results indicate that ECM hydrogel stiffness controls the size of the patterned vasculature and the density of sprouting angiogenesis. RNA sequencing shows that the cellular response to stretching is characterized by the upregulation of certain genes such as ANGPTL4+5, PDE1A, and PLEC.
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spelling doaj.art-3c2cdd3bf6914d0980ff44688f865d7c2023-02-26T04:27:45ZengElsevieriScience2589-00422023-03-01263106198Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chipDario Ferrari0Arunima Sengupta1Lyong Heo2Laszlo Pethö3Johann Michler4Thomas Geiser5Vinicio A. de Jesus Perez6Wolfgang M. Kuebler7Soheila Zeinali8Olivier T. Guenat9Organs-on-chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, SwitzerlandOrgans-on-chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, SwitzerlandStanford Center for Genomics and Personalized Medicine, Palo Alto, CA, USAEmpa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Mechanics of Materials and Nanostructures, Thun, SwitzerlandEmpa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Mechanics of Materials and Nanostructures, Thun, SwitzerlandDepartment of Pulmonary Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, SwitzerlandDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University Medical Center, Stanford, CA, USAInstitute of Physiology, Charité - Universitätsmedizin Berlin, Berlin, GermanyOrgans-on-chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, SwitzerlandOrgans-on-chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland; Department of Pulmonary Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland; Department of General Thoracic Surgery, Inselspital, University Hospital of Bern, Bern, Switzerland; Corresponding authorSummary: The endothelium of blood vessels is a vital organ that reacts differently to subtle changes in stiffness and mechanical forces exerted on its environment (extracellular matrix (ECM)). Upon alteration of these biomechanical cues, endothelial cells initiate signaling pathways that govern vascular remodeling. The emerging organs-on-chip technologies allow the mimicking of complex microvasculature networks, identifying the combined or singular effects of these biomechanical or biochemical stimuli. Here, we present a microvasculature-on-chip model to investigate the singular effect of ECM stiffness and mechanical cyclic stretch on vascular development. Following two different approaches for vascular growth, the effect of ECM stiffness on sprouting angiogenesis and the effect of cyclic stretch on endothelial vasculogenesis are studied. Our results indicate that ECM hydrogel stiffness controls the size of the patterned vasculature and the density of sprouting angiogenesis. RNA sequencing shows that the cellular response to stretching is characterized by the upregulation of certain genes such as ANGPTL4+5, PDE1A, and PLEC.http://www.sciencedirect.com/science/article/pii/S2589004223002754Vascular anatomyBiotechnologyTranscriptomics
spellingShingle Dario Ferrari
Arunima Sengupta
Lyong Heo
Laszlo Pethö
Johann Michler
Thomas Geiser
Vinicio A. de Jesus Perez
Wolfgang M. Kuebler
Soheila Zeinali
Olivier T. Guenat
Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip
iScience
Vascular anatomy
Biotechnology
Transcriptomics
title Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip
title_full Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip
title_fullStr Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip
title_full_unstemmed Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip
title_short Effects of biomechanical and biochemical stimuli on angio- and vasculogenesis in a complex microvasculature-on-chip
title_sort effects of biomechanical and biochemical stimuli on angio and vasculogenesis in a complex microvasculature on chip
topic Vascular anatomy
Biotechnology
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004223002754
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