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Developmental Biology - Cancer 'Switch'
'Painting' Human Stem Cells
Cell membrane re-engineering is a new approach to repairing tissue...
In a world first, scientists find a new way to direct stem cells towards heart tissue. Led by researchers at the University of Bristol these findings, published in Chemical Science, could radically improve the treatment of cardiovascular disease, which causes more than a quarter of all deaths in the UK alone.
To date, trials using stem cells, which are taken and grown from the patient or a donor — and then injected into the patient's heart to regenerate damaged tissue — have produced promising results. However, while these next generation cell therapies are on the horizon, significant challenges remain with how therapeutically generated stem cells redistribute inside our body.
High blood flow in the heart combined with various 'tissue sinks' created by other circulating cells they come into contact with, send the majority of introduced therapeutic stem cells into the patient's lungs and spleen.
Now, researchers from Bristol's School of Cellular and Molecular Medicine have found a way to overcome misdirection by modifying stem cells with a special protein so that cells 'home' onto heart tissue.
Dr Adam Perriman, the study's lead author, explains: "With regenerative cell therapies, where you are trying to treat someone after a heart attack, the cells rarely go to where you want them to go. Our aim is to use this technology to re-engineer the membrane of cells, so that when they are injected, they'll home to specific tissues of our choice.
"We know that some bacterial cells contain properties that enable them to detect and 'home' to diseased tissue. For example, the oral bacterial found in our mouths can occasionally cause strep throat. If it enters the blood stream it can 'home' to damaged tissue in the heart causing infective endocarditis. Our initial aim was to replicate the homing ability of bacterial cells and apply it to stem cells."
Adam Perriman PhD, Associate Professor, Biomaterials, UKRI Future Leaders, Fellow and founder of CytoSeek, a cell therapy technology company; School of Cellular and Molecular Medicine, and BrisSynBio Synthetic Biology Research Centre, University of Bristol, UK.
The team developed the technology by looking at how bacterial cells use a protein called an adhesin to 'home' to heart tissue. Using this protein, researchers produced an artificial cell membrane binding a version of the adhesin that could be 'painted' on the outside of the stem cells. In an animal model, the team were able to demonstrate that this new cell modification technique worked by directing stem cells to the heart in a mouse.
"Our findings demonstrate that cardiac homing properties of infectious bacteria can be transferred to human stem cells. Significantly, we show in a mouse model that designer adhesin protein spontaneously inserted into the plasma membrane of stem cells with no cytotoxity — then directing these modified cells into the heart after transplant.
To our knowledge, this is the first time that targeting properties of infectious bacteria have been transferred to mammalian cells. This new technique carries enormous potential for the seven million people currently living with heart disease in the UK."
Adam Perriman PhD
Abstract
We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of a chimeric protein–polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) binding domain of the bacterial adhesin protein CshA fused to a supercharged protein. Significantly, the protein–polymer surfactant hybrid spontaneously inserts into the plasma membrane of stem cells without cytotoxicity, instilling the cells with a high affinity for immobilized fibronectin. Moreover, we show that this cell membrane reengineering approach significantly improves retention and homing of stem cells delivered either intracardially or intravenously to the myocardium in a mouse model.
Authors
Wenjin Xiao, Thomas I. P. Green, Xiaowen Liang, Rosalia Cuahtecontzi Delint, Guillaume Perry, Michael S. Roberts, Kristian Le Vay, Catherine R. Back, Raimomdo Ascione, Haolu Wang, Paul R. Race and Adam W. Perriman.
Acknowlegements
The Institute for Sustainable Food at the University of Sheffield brings together multidisciplinary expertise and world-class research facilities to help achieve food security and protect the natural resources we all depend on.
Dr Perriman's UKRI Future Leaders fellowship is based on research funded by the Elizabeth Blackwell Institute-funded Catalyst project. Perriman is also a member of the University's BrisSynBio, a multi-disciplinary research centre part of the Bristol BioDesign Institute, which focuses on biomolecular design and engineering aspects of synthetic biology.
Dr Perriman is well-known for his pioneering research on the construction and study of novel synthetic biomolecular systems for regenerative engineering.
The University of Sheffield
With almost 29,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world's leading universities.
A member of the UK's prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines.
Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in.
Sheffield is the only university to feature in The Sunday Times 100 Best Not-For-Profit Organisations to Work For 2018 and for the last eight years has been ranked in the top five UK universities for Student Satisfaction by Times Higher Education.
Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields.
Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, Glaxo SmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.
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Jul 4 2019 Fetal Timeline Maternal Timeline News
 Human mesenchymal stem cells exhibit green fluorescence after being 'painted' by a designer protein. The protein is represented as red, white, and blue molecules. CREDIT University of Bristol.
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