MRC Centre for Regenerative Medicine
Centre profile from the MRC Network publication issued May/June 2008
On 1 March the Centre for Regenerative Medicine at the University of Edinburgh gained full MRC centre status. This award built on the original centre development funding to the Institute for Stem Cell Research, which has now been brought together with clinical and translational scientists from the university’s College of Medicine to create the MRC Centre for Regenerative Medicine. The centre aims to develop therapies for human disease, using stem cells as a starting point.
Research at the centre involves all types of stem cells; adult, embryonic and those found in cord blood, underpinned by basic research efforts. Learning what prompts cells to differentiate and how to control this process is at the heart of future stem cell-based therapies.
The Chancellor’s building, next to the Edinburgh Royal Infirmary, is the home of one part of the new centre. At the moment, research staff are split between there and the Roger Land building on Edinburgh University’s science campus two miles away. A new laboratory due to completed in early 2011, the Scottish Centre for Regenerative Medicine, will unite the research teams, with bench space for 180 scientists.
Grand designs
When Network visited the Director, Professor Sir Ian Wilmut, he described his vision for the future of research on the site: ‘‘We will have a centre working with stem cells, a research hospital with a clinical trials unit, Edinburgh University’s teaching and research facilities, basic research scientists and biotechnology companies in one location. I think that’s a unique combination with huge potential for translational research but also for the use of stem cells in drug discovery and development work. It will be a unique resource in the UK.’’
This collaborative potential is reflected in the design of the new laboratory. Centre manager Dr Gordon McLean outlined plans: “The new building has been designed to remove as many of the corridors and most of the walls, creating an open-plan environment designed to facilitate and promote interaction and collaboration. There will be a centralised tissue culture facility surrounded by lab space separated from the write-up desk space by a floor-to-ceiling glass wall, so there will be plenty of opportunities to share ideas.’’
Repairing bones
Currently at the centre, Dr Brendon Noble, director of the Musculoskeletal Tissue Engineering Collaboration, is investigating bone and cartilage repair. He is keen to stress that stem cells are the starting point for the development of therapy: ‘‘We need to regenerate and mend things, effectively we want to repair the skeleton using what we know about stem cells, those that are already in the person or those manufactured in the laboratory and put back in. Both approaches are important.’’ In the long term, Brendon hopes therapies derived from stem cells could be used to strengthen slow-healing bone fractures or repair torn cartilage.
At the moment, he’s trying to find out how to keep cells alive and active when they are put back into bone where other cells have died or become inactive. ‘‘One of our preoccupations is ageing,’’ he explained. ‘‘The environment within the body changes hugely as you age. If you take stem cells out of a 90 year-old person and put them in a dish in the lab they grow fantastically but they are relatively inactive in the body. The media we use to grow cells in a dish is simple to control and is very different to an ageing body. We need to learn how to support cells to keep them alive when you put them back into the bone and we are using carriers or scaffolds that re-create a supportive environment for the cells.’’ Already, a research programme using adult stem cells taken from damaged tissue, modified in the lab and re-introduced to the body is showing promise in pre-clinical models. It is hoped this work will go into a patient clinical trial after another two years of development.
Encouraging stem cells to specialise involves controlling gene expression and this can be achieved without gene therapy by exposure to hormones or signalling molecules and even subtle adaptations to the surface of whatever the cells are growing on. So Brendon is also collaborating with a microelectronics group that has expertise in building silicon chips. These are used to make cell-media surfaces with the right features to encourage cells to specialise into the required type of cell.
Stem cells and the thymus
Over in the Roger Land building, the target of Dr Clare Blackburn’s work is less well known. The thymus, a small organ lodged above the heart, influences the body’s ability to respond to infection by producing virus-fighting T cells. Like bone, with age the thymus loses its potency and so the ability to mount new immune responses diminishes.
Clare explained: ‘‘The thymus is one of the first organs to degenerate, it’s thought to begin in teenage years and by the time a person is 30 to 40 years old the organ has shrunk and the whole structure has changed, so fewer new T cells are produced.’’
By transplanting cells from the developing thymus of a mouse embryo to the kidney capsule of another mouse, her team has been able to grow a whole functioning thymus in the capsule’s supportive environment.
‘‘The cells transplanted from a mouse embryo are already restricted to becoming the thymus. What we are interested in is how these cells arise, what stimulates the organ to form where it does and what limits the size of it. Learning how to boost thymus function could help boost immunity,’’ said Clare. The most likely clinical application is in bone marrow transplant patients. Clare added: “The treatments adults are given before a bone marrow transplant knock out what is left of the thymus so they are in a poor position to reconstitute their immune system after the transplant. This is one of the major causes of mortality after an adult has had a bone marrow transplant”.
Clare recognises that communicating with the public about her work is an important part of what she does, and has contributed to three short films about stem cells used in public engagement work.
Blood stem cells and transplants
Next door, Professor Alexander Medvinsky is investigating the development of haematopoietic (blood) stem cells, those that give rise to all blood cells throughout a person’s life. When a patient receives chemotherapy or radiation to destroy cancer cells, blood cells are destroyed too and so this system needs to be restored with a bone marrow transplant. Haematopoietic stem cells are important clinically because they are responsible for the successful outcome of bone marrow transplants.
Alexander explained: ‘‘The problem is that bone marrow transplants are not always easily available. There is a shortage of matching donors, and so it would be desirable to produce haematopoietic stem cells in the lab so that we could create a bank of cells for transplantations.’’
There are challenges to overcome. At the moment blood cells can be produced from embryonic stem cells in the lab but they are weak and in experiments using mice they haven’t shown the same restorative ability as naturally occurring blood stem cells. Alexander and his team are currently using a mouse model to learn how to improve the potency of lab cultured cells.
In future research he hopes to investigate how the potential of haematopoietic stem cells in the umbilical cord can be enhanced and wishes to develop new lab protocols to achieve this. Cord blood is a well known source of stem cells and has been used in transplants between siblings to repair the blood cell system of the older child.
Light micrograph of a human embryo at the two-cell stage of development
Leading the field
Other research at the centre is focused on understanding the properties of stem cells, how to control stem cell self-renewal and differentiation in vitro and in vivo, and how to harness this knowledge to develop new therapies.
For all the scientists working under the umbrella of the MRC Centre for Regenerative Medicine, the route to developing therapies based on stem cells is challenging. But with the facilities and collaborative opportunities that will soon be on offer, they are well placed to lead the field of regenerative medicine into therapy for patients.
