Primary human lung pericytes support and stabilize in-vitro perfusable microvessels.

Bichsel, Colette Andrea; Hall, Sean; Schmid, Ralph; Guenat, Olivier Thierry; Geiser, Thomas (2015). Primary human lung pericytes support and stabilize in-vitro perfusable microvessels. Tissue engineering. Part A, 21(15-16), p. 2166. Mary Ann Liebert 10.1089/ten.TEA.2014.0545

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The formation of blood vessels is a complex tissue-specific process that plays a pivotal role during developmental processes, in wound healing, cancer progression, fibrosis and other pathologies. To study vasculogenesis and vascular remodeling in the context of the lung, we developed an in-vitro microvascular model that closely mimics the human lung microvasculature in terms of 3D architecture, accessibility, functionality and cell types. Human pericytes from the distal airway were isolated and characterized using flow cytometry. To assess their role in the generation of normal microvessels, lung pericytes were mixed in fibrin gel and seeded into well-defined microcompartments together with primary endothelial cells (HUVEC). Patent microvessels covering an area of 3.1 mm2 formed within 3-5 days and were stable for up to 14 days. Soluble signals from the lung pericytes were necessary to establish perfusability, and pericytes migrated towards endothelial microvessels. Cell-cell communication in the form of adherens and tight junctions, as well as secretion of basement membrane was confirmed using transmission electron microscopy and immunocytochemistry on chip. Direct co-culture of pericytes with endothelial cells decreased the microvascular permeability by one order of magnitude from 17.8∙10-6 cm/s to 2.0∙10-6 cm/s and led to vessels with significantly smaller and less variable diameter. Upon phenylephrine administration, vasoconstriction was observed in microvessels lined with pericytes but not in endothelial microvessels only. Perfusable microvessels were also generated with human lung microvascular endothelial cells and lung pericytes. Human lung pericytes were thus shown to have a prominent influence on microvascular morphology, permeability, vasoconstriction and long-term stability in an in-vitro microvascular system. This biomimetic platform opens new possibilities to test functions and interactions of patient-derived cells in a physiologically relevant microvascular setting.

Item Type:

Journal Article (Original Article)

Division/Institute:

10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research > ARTORG Center - Lung Regeneration Technologies
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) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bichsel, Colette Andrea; Hall, Sean; Schmid, Ralph; Guenat, Olivier Thierry and Geiser, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1937-3341

Publisher:

Mary Ann Liebert

Language:

English

Submitter:

Olivier Thierry Guenat

Date Deposited:

03 Jun 2015 15:35

Last Modified:

19 Apr 2016 02:30

Publisher DOI:

10.1089/ten.TEA.2014.0545

PubMed ID:

25891384

BORIS DOI:

10.7892/boris.68263

URI:

https://boris.unibe.ch/id/eprint/68263

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