#endothelial cells

[ricisidro]

SARS-CoV-2 attacks nearly every organ system of the body including the blood vessel wall linings (endothelial cells), causing inflammation that may lead to blood clots blocking blood flow and causing a particular disease - a key to multi-organ complications of Covid and Long Covid, published in the Science journal on November 28, 2024.

https://www.science.org/doi/10.1126/science.add2962

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Magnetic Morphing

Using magnetic forces to remotely shape 3D printed hydrogel scaffolds with biomedical applications such as for growing endothelial cells in vessel networks (pictured)

Read the published research paper here

Image from work by Ruoxiao Xie and Yuanxiong Cao, and colleagues

Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London and Department of Physiology, Anatomy and Genetics, Kavli Institute for Nanoscience Discovery, University of Oxford, UK

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Science Advances, February 2024

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[currentsinbiology]

A Recipe to Make a Human Blood-Brain Barrier

The blood-brain barrier is the brain’s gatekeeper. A nearly impenetrable shield of cells, it keeps toxins and other agents that may be in circulating blood from gaining access to and harming the brain.

A critical anatomical structure, the barrier is the brain’s first and most comprehensive line of defense. But in addition to protecting the brain, it also is involved in disease and effectively blocks many of the small-molecule drugs that might make effective therapies for a host of neurological conditions, including such things as stroke, trauma and cancer.

Rudimentary models of the barrier have been created in the laboratory dish using human stem cells, but such models have depended on mixing a cocktail of cell types to elicit the complex chemical interplay that directs blank slate stem cells to become the endothelial cells that make up the blood-brain barrier.

In a report published this week (Nov. 8, 2017) in Science Advances, researchers from the University of Wisconsin-Madison detail a defined, step-by-step process to make a more exact mimic of the human blood-brain barrier in the laboratory dish. The new model will permit more robust exploration of the cells, their properties and how scientists might circumvent the barrier for therapeutic purposes.

“The main advance is we now have a fully defined process that uses small molecules to guide cells through the developmental process,” says University of Wisconsin-Madison Professor of chemical and biological engineering Sean Palecek of the method that substitutes chemical factors for cells to push stem cells to become the brain endothelial cells that compose the blood-brain barrier. “It is fully defined. We know what components are acting on the cells” and at what stages of development.

 Full open access research for “Directed differentiation of human pluripotent stem cells to blood-brain barrier endothelial cells” by Tongcheng Qian, Shaenah E. Maguire, Scott G. Canfield, Xiaoping Bao, William R. Olson, Eric V. Shusta and Sean P. Palecek in Science Advances. Published online November 8 2017 doi:10.1126/sciadv.1701679

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Older and Leakier

Homing in on inflamed tissues in live mice by high-resolution microscopy reveals that inflammation is promoted by senescent [biologically old] cells lining the blood vessels

Read the published research article here

Still from a video from work by Loïc Rolas and Monja Stein, and colleagues

Centre for Microvascular Research, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in EMBO Reports, June 2024

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[ricisidro]

Review of organ damage such as the heart, brain, endothelial cells and blood vessels, endocrine system, and immune system (see photo) from COVID and Long COVID: a disease with a spectrum of pathology, published in the Medical Journal, 2 July 2024.

"there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections."

https://www.degruyter.com/document/doi/10.1515/mr-2024-0030/html

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Brain Bug

Bacterial meningitis is life-threatening. Caused by infection of the brain coverings (meninges) with bacteria, such as E.coli, it's especially deadly in infants. Using mice, researchers investigate how cells in the meninges respond to E.coli infection soon after birth. Upon infection, single nucleus RNA sequencing revealed macrophages, fibroblasts and endothelial cells, which line blood vessels, significantly changed their gene activity. Endothelial cells increased the activity of TLR4, a signalling protein. In mice lacking TLR4, the response to infection was weakened. Next, the team dissected different layers of the meninges – the dura (pictured, top left) and leptomeninges (top right, bottom) – to image cell junction (green, red) and blood-brain barrier proteins (pink). Infection caused proteins normally found at cell junctions in leptomeninges endothelial cells to redistribute elsewhere and leptomeninges capillaries to become disorganised and leaky. This provides insights into how the meninges blood vessel network responds to infection.

Written by Lux Fatimathas

Image from work by Jie Wang, Amir Rattner and Jeremy Nathans

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, June2023

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Leading Edge

Protein called SAM68 plays a key role in blood vessel wall cell (endothelium) interaction with the extracellular matrix regulating cell remodelling and migration

Read the published research paper here

Image from work by Zeinab Rekad and colleagues

Université Côte d'Azur, CNRS, INSERM, iBV, Nice, France

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, August 2023

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Stopping Sprouts

Like roads in a city, veins in your body need careful mapping. When they don’t stick to the plan, sporadic vascular malformation – malformed veins – occur, causing pain and disfigurement. These veins form lesions containing genetically faulty cells (mutants). Currently, lesions often recur after treatment. Researchers now search for new therapeutics by growing mutant endothelial cells (ECs), collected from the veins of patients, in dishes. RNA sequencing revealed mutant ECs produced the signalling molecule TGFa. Fluorescence microscopy revealed when supporting cells from lesions (stromal cells) were grown alongside normal ECs, they triggered more EC sprouting (pictured, middle, right) compared with non-lesion stromal cells (left). Next, by grafting mutant ECs into mice, they found EC-produced TGFa triggered stromal cells to release the signalling molecule VEGFA. This caused EC sprouting and malformed veins. Treating mice with afatinib, a drug that interferes with VEGF signalling, decreased lesions, suggesting it may be a useful therapeutic.

Written by Lux Fatimathas

Image from work by Suvi Jauhiainen and Henna Ilmonen, and colleagues

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, May 2023

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