Professor Stelios Andreadis Paper Accepted in Nature Communications
Published April 8, 2020
SUNY Distinguished Professor Stelios Andreadis was recently published in Nature Communications. The piece is titled "Endothelialization of arterial vascular grafts by circulating monocytes."
Project Overview
Monocytes (a type of white blood cell) are usually associated with host defense against pathogens. However, these specialized cells are also critical players in tissue homeostasis- responding to stimuli to either break down or regenerate tissue. Until now it was understood that monocytes participate in tissue regeneration indirectly by producing pro-regeneration factors that stimulate other cell types to regenerate the tissue. In this study it was found that the monocytes can also directly contribute to regeneration within the context of blood vessels.
Dr. Andreadis' laboratory developed cell-free vascular grafts that can be used as replacements of damaged or clotted arteries. When implanted into the arterial system of a pre-clinical ovine (sheep) animal model, they remained patent (open, non-thrombosed) and integrated with the host vasculature. The lumen of blood vessels is lined with a specialized type of cell called an endothelial cell that is necessary for preventing thrombosis and keeping them healthy. Therefore, it would be expected that cells covering the lumen of the implanted grafts would originate from the adjoining native artery. To their surprise, the research group found that instead of endothelial cells, blood monocytes attached to the graft lumen and under the influence of biochemical factors such as the vascular endothelial growth factor (VEGF) that was immobilized on the lumen; as well as biophysical factors, such as shear stress from flowing blood, they turned into endothelial-like cells that kept the grafts patent and functional. This study demonstrates the plasticity of monocytes that can trans-differentiate into endothelial cells and regenerate arterial vessels. Given the abundance of monocytes in the blood (they represent ~ 20% of white blood cells), this discovery has important implications in the field of regenerative medicine, as it identifies a novel means of promoting blood vessel growth and possibly contributing to the repair of cardiovascular tissues in-vivo following endothelial disruption by disease or injury (e.g. catheterization).
The figures below show monocytes differentiated on VEGF surfaces using our optimized protocol and further subjected to physiological shear differentiate to a mature endothelial phenotype.
Immunostaining shows expression of key monocyte/macrophage and endothelial markers on monocyte derived endothelial cells after exposure to physiological shear on an immobilized VEGF surface: (left) CD163 (red) and CD144 (green); (right) CD31 (red) and CD14 (green).; (n, r) White arrows indicate the direction of fluid flow.
Single cell RNA sequencing and bioinformatic analysis shows that monocyte derived endothelial cells (MCEC) are genetically similar to human carotid artery endothelial cells (HCAEC) and are distinct from their monocytic (MC) origins.
This finding is published in Nature Communications, which is a bimonthly peer-reviewed scientific journal published by the Nature Publishing Group with an impact factor of 12. [Read the full paper]
