̽��ֱ�� of Cambridge - Athina Markaki

Artificial bile ducts grown in lab and transplanted into mice could help treat liver disease in children

cjb250 — Mon, 03 Jul 2017 15:11:08 +0000

In research published in the journal Nature Medicine, the researchers grew 3D cellular structure which, once transplanted into mice, developed into normal, functioning bile ducts.

Bile ducts are long, tube-like structures that carry bile, which is secreted by the liver and is essential for helping us digest food. If the ducts do not work correctly, for example in the childhood disease biliary atresia, this can lead to damaging build of bile in the liver.

̽��ֱ��study suggests that it will be feasible to generate and transplant artificial human bile ducts using a combination of cell transplantation and tissue engineering technology. This approach provides hope for the future treatment of diseases of the bile duct; at present, the only option is a liver transplant.

̽��ֱ�� ̽��ֱ�� of Cambridge research team, led by Professor Ludovic Vallier and Dr Fotios Sampaziotis from the Wellcome-MRC Cambridge Stem Cell Institute and Dr Kourosh Saeb-Parsy from the Department of Surgery, extracted healthy cells (cholangiocytes) from bile ducts and grew these into functioning 3D duct structures known as biliary organoids. When transplanted into mice, the biliary organoids assembled into intricate tubular structures, resembling bile ducts.

̽��ֱ��researchers, in collaboration with Mr Alex Justin and Dr Athina Markaki from the Department of Engineering, then investigated whether the biliary organoids could be grown on a ‘biodegradable collagen scaffold’, which could be shaped into a tube and used to repair damaged bile ducts in the body. After four weeks, the cells had fully covered the miniature scaffolding resulting in artificial tubes which exhibited key features of a normal, functioning bile duct. These artificial ducts were then used to replace damaged bile ducts in mice. ̽��ֱ��artificial duct transplants were successful, with the animals surviving without further complications.

“Our work has the potential to transform the treatment of bile duct disorders,” explains Professor Vallier. “At the moment, our only option is liver transplantation, so we are limited by the availability of healthy organs for transplantation. In future, we believe it will be possible to generate large quantities of bioengineered tissue that could replace diseased bile ducts and provide a powerful new therapeutic option without this reliance on organ transplants.”

“This demonstrates the power of tissue engineering and regenerative medicine,” adds Dr Sampaziotis. “These artificial bile ducts will not only be useful for transplanting, but could also be used to model other diseases of the bile duct and potentially develop and test new drug treatments.”

Professor Vallier is part of the Department of Surgery at the ̽��ֱ�� of Cambridge and his team are jointly based at the Wellcome Trust-MRC Cambridge Stem Cell Institute and the Wellcome Trust Sanger Institute.

̽��ֱ��work was supported by the Medical Research Council, Sparks children’s medical research charity and the European Research Council.

Reference
Sampaziotis, F et al. Reconstruction of the murine extrahepatic biliary tree using primary extrahepatic cholangiocyte organoids. Nature Medicine; 3 July 2017; DOI: 10.1038/nm.4360

Cambridge scientists have developed a new method for growing and transplanting artificial bile ducts that could in future be used to help treat liver disease in children, reducing the need for liver transplantation.

Our work has the potential to transform the treatment of bile duct disorders

Ludovic Vallier

Fotis Sampaziotis

mage of a mouse gallbladder following repair with a bioengineered patch of tissue incorporating human 'bile duct' cells, shown in green. ̽��ֱ��human bile duct cells have fully repaired and replaced the damaged mouse epithelium

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Closing the Gender Gap

ta385 — Fri, 02 Oct 2015 11:00:00 +0000

Gender diversity, both in education and the economy, is now the subject of serious debate among policy-makers, academics, teachers and employers. Of particular concern is the fact that female participation in STEM subjects – science, technology, engineering and mathematics – suffers from a “leaky pipeline”. Up to the age of sixteen, as many girls as boys study maths and science, but thereafter a gap opens up which continues to widen at each step of the career ladder.

For this reason, many of Cambridge’s access events aim to encourage female students, particularly those in state sector schools and colleges, to continue studying mathematics and science at school and to apply for university courses in which women are currently under-represented across the UK.

Recent events have included

Robinson College’s Women in Science Festival

Robinson welcomed 124 female Sixth Formers from across the country to its inaugural Women in Science Festival, an entirely free one day event aimed at encouraging more young women to pursue further study in science and maths related disciplines.

̽��ֱ��event opened with five talks by female scientists currently making waves at Cambridge. Dr Liisa Van Vliet spoke about microscopy, Dr Teresa Tiffert on Malaria and Anaemias and Dr Athina Markaki on Cardiovascular stents. They were followed by two PhD students – Joana Grah discussed the use of Mathematical Image Analysis in Cancer Research while Diana Vasile revealed the computer science behind mobile devices.

Twelve courageous Sixth Formers then took to the stage to give five minute presentations about a STEM topic which they feel passionate about, earning feedback from an expert judging panel. After taking lunch at Robinson with College Fellows and students, the participants visited the Department of Materials Science & Metallurgy to experience ̽��ֱ��-level laboratory work. ̽��ֱ��most popular experiment involved measuring the temperature-dependent properties of rubber, with the participants using liquid nitrogen to cool their samples.

Robinson’s Dr Rachel Oliver, a Reader in Materials Science, said "We believe that many young women have the potential to make a real contribution in STEM subjects, but they are sometimes put off by misconceptions about science and engineering, or about the people who work in those fields. We wanted to give Sixth Formers the opportunity to meet real female scientists and engineers and be inspired by the work they do.”

Gonville & Caius College’s Women in Economics Day

Highly respected female economists including Dame Kate Barker, a former member of the Bank of England’s Monetary Policy Committee, and Dr Vicky Pryce, former joint head of the Government Economic Service, gave 100 Sixth Form girls a clear message: “Economics Needs You!”

Women currently represent about 36% of applications to study economics at Cambridge and receive 37 per cent of offers. This is significantly higher than the UK average. A recent study by the ̽��ֱ�� of Southampton found that women account for just 27 per cent of economics students in the UK, despite making up 57 per cent of the overall undergraduate population. Nevertheless, the Collegiate ̽��ֱ�� would like to see more women studying Maths in Sixth Form and going on to apply to study economics.

̽��ֱ��event at Gonville & Caius was run by Dr Victoria Bateman, Director of Studies for Economics at the College. Dr Bateman told a packed auditorium "Sadly, the lack of female representation in the subject has meant that economists have built a model of the economy which tells only half of the story. ̽��ֱ��future of economics – and the economy – is in your hands.”

̽��ֱ��students received a welcome message from Carolyn Fairbairn, who gained a double first in economics at Caius and becomes the CBI’s first female director general in November 2015. Ms Fairbairn said economics was too often seen as “a science that only an elite of often male experts are qualified to comment on” and argued that women’s views were vital if economic policy were to respond to the needs of both genders.

Corpus Christi College’s STEM Summer School for Years 12 & 13

For the first time, Corpus Christi ran a three-day STEM event for 16-18 year old female students from across the country. 86 schools, the vast majority state sector, selected one hundred participants to take part in recognition of their impressive academic achievements and their passion for one or more of the STEM subjects.

̽��ֱ��event combined hands-on activities, departmental visits and lectures on a diverse range of topics, from the chemistry of water to a programming language for blind children. It also included a practical advice session on STEM interviews at Cambridge.

Unforgettable words of encouragement came from Dame Athene Donald, Professor of Experimental Physics and Master of Churchill College, Cambridge, who spoke of the importance of perseverance and the increasingly interdisciplinary nature of the sciences.

Event leader, Dr Sophie Zadeh, Fellow in Psychology at Corpus Christi College, said “We’re thrilled that we’ve been able to offer these young women the opportunity to experience Cambridge but we want to ensure the impact of this event reaches far beyond the attendees. We want to help close the gender gap in STEM across the country.”

More information and photos here.

Newnham College’s Joan Clarke Maths Residential

Joan Clarke achieved a double first in Mathematics at Newnham in the 1930s and went on to play a crucial role in the Second World War by helping to crack the Enigma machine at Bletchley Park.

Named in her honour, Newnham’s inaugural maths residential gave thirty Year 13s studying Further Maths at state schools an inspiring taste of STEM subjects at Cambridge.

̽��ֱ��programme included lectures, seminars, discussion groups, practical work and social activities, as well as the opportunity to meet current staff and students.

This entirely free event was made possible by alumnae donations made specifically to encourage more women from state schools to apply for science and maths based courses at Cambridge.

Dr Sam Lucy, Newnham’s Admissions Tutor, said: “This initiative gives very bright young women the information they need to make competitive applications to Cambridge and other top universities, while also helping them to explore the different types of maths taught on STEM courses."

More information here.

Murray Edwards College’s ‘She Talks Science’

Murray Edwards recently set up ‘She Talks Science’, a blog designed to give young women the opportunity to share their passion for science with each other and with Murray Edwards students, Fellows and alumnae. Previous posts have included thoughts on snowflakes, micro-seismic activity and an inspiring introduction from the College’s President, Barbara Stocking.

̽��ֱ��College’s annual Pathways to Success conference introduces high-achieving Year 12s from schools across the UK to students, graduates and staff at Murray Edwards. ̽��ֱ��event aims to encourage young women to expand their horizons and to embrace aiming high. Previous guest speakers have included high-flying alumnae who studied science at the College.

Cavendish Inspiring Women (CiW)

CiW was set up by two Cambridge PhD students, Sarah Morgan and Hannah Stern, together with Dr Elsa Couderc, a former post-doc at the ̽��ֱ��, and Dr Atefey Amin, a research associate, to encourage young women to pursue careers in science, or to use their science training to further other career paths.

CiW introduces promising teenage scientists to inspiring role models by holding regular speaker events at the Cavendish Laboratory. Previous speakers have included Dr Sarah Bohndiek, a lecturer in biomedical physics and a junior research group leader at the Cancer Research UK Cambridge Institute. CiW also provides advice via its website and recently published ‘What is so Exciting About Physics?’ a free booklet aimed at secondary school students featuring insights from several female scientists.

Hannah and Sarah said “We both really enjoy studying science and haven't felt disadvantaged by being women. But we have noticed how few female scientists there are in comparison to men and we know that the way society portrays scientists can sometimes be very stereotypical. So we started Cavendish Inspiring Women to promote the visibility of women in science and to show that it can be an excellent career path for women as well as men.”

Every year, 200,000 young people participate in access initiatives run by the ̽��ֱ�� and the Colleges. This programme includes a wide range of opportunities specifically designed to inspire young women and to foster greater participation in certain areas of Higher Education and work.

"We promote the visibility of women in science and show that it can be an excellent career path for women as well as men".

Sarah Morgan & Hannah Stern, Cavendish Inspiring Women

Robinson College’s Women in Science Festival

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Magneto-active porous materials get close to the bone

bjb42 — Sat, 01 May 2010 00:00:00 +0000

Prosthetic implants provide long-term pain relief for many millions of people worldwide – in the UK alone, 160,000 hip and knee replacement operations were carried out in 2009 – and, as people live longer, the demand will continue to grow. Typical lifetimes of artificial joints are only about 10–15 years, with the most common cause of failure being loosening of the prosthesis stem from where it embeds into the bone. Once a joint becomes loose, wear debris tends to form and cause damage. Therefore, ensuring that the bond between bone and implant remains strong is an important objective.

An innovative solution that is being investigated by Dr Athina Markaki in the Department of Engineering may provide an answer. ̽��ֱ��aim is to promote early bone ingrowth into the surface of the prosthesis and anchor it securely.

Bare bones of the matter

Bone is an active material, responding to stresses and strains within. It’s long been known that mechanical strain, such as occurs during exercise, encourages bone modelling (formation) and remodelling (resorption). In fact, this forms the basis of the physiotherapeutic exercise commonly applied after implantation. However, in cases where the patient requires complete immobilisation, such treatments are clearly impossible, and drugs are often the only alternative. If a therapy could be devised in which controlled levels of mechanical strain are induced directly within ingrowing bone via the prosthesis itself, this would improve the bonding between prosthesis and bone, and avoid the danger of loosening caused by premature excessive exercise.

Engineering solutions

Dr Markaki’s project focuses on a novel concept called magneto-mechanical actuation, which arose from work she carried out with Professor Bill Clyne at the Department of Materials Science and Metallurgy in Cambridge, funded by the Cambridge-MIT Institute. It involves a porous surface layer made of ferromagnetic fibres that is attached to a conventional prosthesis and promotes ingrowth of bone so as to anchor it more fully and rapidly. Porous metal implants are not new. ̽��ֱ��innovative concept here is that mechanical strain is generated in the bone by applying a magnetic field. This causes the network of ferromagnetic fibres to move so as to align with the field, imposing strains on bone cells as they grow into the network.

Modelling of the phenomenon has shown that the degree of strain is determined by the geometry of the network – in other words, the prosthesis can be coated with material that is tailor-made to impart the optimum strain on ingrowing bone to promote growth. Once the optimum exposure regimes have been established, the idea is to apply a magnetic field during the postoperative period to the region of the implant. ̽��ֱ��strength of the field would be lower than that currently used for diagnostic purposes, such as in magnetic resonance imaging, but would be sufficient to cause the fibres to move.

Thanks to a recent award of a €1.5 million European Research Council Starting Investigator grant, Dr Markaki has embarked on a five-year programme to progress this concept to application. ̽��ֱ��work will be carried out in close collaboration with Dr Roger Brooks at Cambridge’s Department of Surgery (Orthopaedic Research Unit). ̽��ֱ��hope is that the technique will yield a new generation of longer-lasting and more durable prosthetic implants, reducing the painful and costly need for replacements.

For more information, please contact Dr Athina Markaki (am253@cam.ac.uk) at the Department of Engineering.

̽��ֱ��most common cause of artificial joint failure is loosening of the prosthetic implant. Dr Athina Markaki is designing materials to anchor them securely.

̽��ֱ��innovative concept here is that mechanical strain is generated in the bone by applying a magnetic field. 

Harshpatel;Photographer on flickr

Magnet

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