Fluid Flow Regulation of Revascularization and Cellular Organization in a Bioengineered Liver Platform

Tissue Engineering. Part C, Methods
Pedro M BaptistaShay Soker

Abstract

Modeling of human liver development, especially cellular organization and the mechanisms underlying it, is fundamental for studying liver organogenesis and congenital diseases, yet there are no reliable models that mimic these processes ex vivo. Using an organ engineering approach and relevant cell lines, we designed a perfusion system that delivers discrete mechanical forces inside an acellular liver extracellular matrix scaffold to study the effects of mechanical stimulation in hepatic tissue organization. We observed a fluid flow rate-dependent response in cell distribution within the liver scaffold. Next, we determined the role of nitric oxide (NO) as a mediator of fluid flow effects on endothelial cells. We observed impairment of both neovascularization and liver tissue organization in the presence of selective inhibition of endothelial NO synthase. Similar results were observed in bioengineered livers grown under static conditions. Overall, we were able to unveil the potential central role of discrete mechanical stimulation through the NO pathway in the revascularization and cellular organization of a bioengineered liver. Last, we propose that this organ bioengineering platform can contribute significantly to the identifi...Continue Reading

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Citations

Oct 12, 2017·Tissue Engineering. Part a·Wessam HassaneinJohn C LaMattina
Sep 20, 2018·Advanced Healthcare Materials·Cécile LegallaisDimitrios Stamatialis
Aug 24, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Dipen VyasShay Soker
Dec 7, 2018·Journal of Biomedical Materials Research. Part a·Fanwei MengDieter Broering
Feb 13, 2018·Gastroenterology·Chen ChenBart Spee

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Methods Mentioned

BETA
Assay
ELISA
PCR

Software Mentioned

Graphpad Prism

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