Dataset Information

A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions.

ABSTRACT: Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of the native tissue nor do they allow examination of cell-cell interactions under relevant hemodynamic conditions. Here, we describe a 3D microfluidic chip model of arterial endothelial and smooth muscle cells where cellular organization, composition and interactions, as well as the mechanical environment of the arterial wall are mimicked. The hemodynamic EC-VSMC-signalling-on-a-chip consists of two parallel polydimethylsiloxane (PDMS) cell culture channels, separated by a flexible, porous PDMS membrane, mimicking the porosity of the internal elastic lamina. The hemodynamic EC-VSMC-signalling-on-a-chip allows co-culturing of human aortic endothelial cells (ECs) and human aortic vascular smooth muscle cells (VSMCs), separated by a porous membrane, which enables EC-VSMC interaction and signalling, crucial for the development and homeostasis of the vessel wall. The device allows real time cell imaging and control of hemodynamic conditions. The culture channels are surrounded on either side by vacuum channels to induce cyclic strain by applying cyclic suction, resulting in mechanical stretching and relaxation of the membrane in the cell culture channels. The blood flow is mimicked by creating a flow of medium at the EC side. Vascular cells remain viable during prolonged culturing, exhibit physiological morphology and organization and make cell-cell contact. During dynamic culturing of the device with a shear stress of 1-1.5 Pa and strain of 5-8%, VSMCs align perpendicular to the given strain in the direction of the flow and EC adopt a cobblestone morphology. To our knowledge, this is the first report on the development of a microfluidic device, which enables a co-culture of interacting ECs and VSMCs under hemodynamic conditions and presents a novel approach to systematically study the biological and mechanical components of the intimal-medial vascular unit.

SUBMITTER: van Engeland NCA

PROVIDER: S-EPMC5972738 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions.

van Engeland Nicole C A NCA Pollet Andreas M A O AMAO den Toonder Jaap M J JMJ Bouten Carlijn V C CVC Stassen Oscar M J A OMJA Sahlgren Cecilia M CM

Lab on a chip 20180501 11

Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions. Current 3D vessel wall constructs do not recapitulate the mechanical conditions of the native tissue nor do they allow examination of cell-cell interactions under relevant hemodynamic conditions. Here, we describe a 3D microfluidic chip model of arterial endothelial and smooth muscl ...[more]

PMID: 29756630

Similar Datasets

Project description:Therapeutic delivery from microvasculature to cancerous sites is influenced by many factors including endothelial permeability, vascular flow rates/pressures, cancer secretion of cytokines and permeabilizing agents, and characteristics of the chosen therapeutics. This work uses bi-layer microfluidics capable of studying dye and therapeutic transport from a simulated vessel to a cancerous region while allowing for direct visualization and quantification of endothelial permeability. 2.5 to 13 times greater dye transport was observed when utilizing small dye sizes (FITC) when compared to larger molecules (FITC-Dextran 4?kDa and FITC-Dextran 70?kDa), respectively. The use of lower flow rates/pressures is shown to improve dye transport by factors ranging from 2.5 to 5 times, which result from increased dye diffusion times within the system. Furthermore, subjecting confluent endothelial monolayers to cancerous cells resulted in increased levels of vascular permeability. Situations of cancer induced increases in vascular permeability are shown to facilitate enhanced dye transport when compared to non-diseased endothelial monolayers. Subsequent introduction of paclitaxel or doxorubicin into the system was shown to kill cancerous cells resulting in the recovery of endothelial confluency overtime. The response of endothelial cells to paclitaxel and doxorubicin is quantified to understand the direct influence of anti-cancer therapeutics on endothelial growth and permeability. Introduction of therapeutics into the system showed the recovery of endothelial confluency and dye transport back to conditions experienced prior to cancer cell introduction after 120?h of continuous treatment. Overall, the system has been utilized to show that therapeutic transport to cancerous sites depends on the size of the chosen therapeutic, the flow rate/pressure established within the vasculature, and the degree of cancer induced endothelial permeability. In addition, treatment of the cancerous region has been demonstrated with anti-cancer therapeutics, which are shown to influence vascular permeability in direct (therapeutics themselves) and indirect (death of cancer cells) manners. Lastly, the system presented in this work is believed to function as a versatile testing platform for future anti-cancer therapeutic testing and development.

Dataset Information

A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions.

Publications

A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets