Spotlight on: Regenerative medicine
What is regenerative medicine?
Age-related macular degeneration (AMD) is the most common cause of sight loss in the UK and can lead to a rapid loss of central (reading) vision. The first patients to receive a specially engineered patch of retinal pigment epithelium cells derived from stem cells to treat severe sight loss from wet AMD regained their reading vision. This stem cell technology was developed with MRC funding.
This ground-breaking clinical study is an example of regenerative medicine – a branch of science that seeks to repair or replace damaged and diseased human cells and tissues. These results are the first description of a complete engineered tissue that has been successfully used in this way and it’s hoped that it will also help treat dry AMD in the future.
The value of stem cells
At the heart of regenerative medicine is research using stem cells. These are cells that can regenerate almost indefinitely. Some, known as pluripotent stem cells, can develop into any of the cell types in the body. This extraordinary flexibility means they have the potential to treat many different diseases and conditions that currently have no cure, like type 1 diabetes, blindness, Parkinson’s disease, heart disease and arthritis.
Creating new cells to replace dead or damaged tissue is known as stem cell therapy. Professor Robin Ali is an MRC-funded scientist at University College London who is exploring the use of stem cell therapy for restoring eyesight in patients with degenerative retinal disease. By producing new, healthy retinal cells and injecting them into a patient with the disease, Robin hopes to find out if the therapy will be safe and effective to use in future. So far it has been successfully tested in mice, and now Robin’s work is moving towards clinical trials. “There’s little more we can learn by treating another mouse. The most exciting science now is in patients and seeing just how effectively the technology can work in people,” says Robin.
Stem cells are also being used to improve our understanding of how degenerative diseases develop and progress. This will help scientists to find drugs that can slow down the symptoms of these diseases, prevent them from getting worse, and even reverse them. A specific type of adult stem cell, called an induced pluripotent stem (iPS) cell, is essential to this work. iPS cells are created from ordinary skin, blood or hair cells by ‘winding back the clock’ and reprogramming them to become stem cells. They are then able to develop into many different cell types that can be used in the lab to study disease. This approach has been used to recreate nerve cells from patients who are suffering with conditions like Parkinson’s and Alzheimer’s disease, and cardiac cells from patients with heart disease. Scientists can study these cells more closely and use them to develop and test drugs – something which is impossible to do in living patients.
From the lab to the clinic
Research in regenerative medicine is already having a huge impact in the clinic. Though sometimes overlooked, bone marrow transplants using blood stem cells are a well-established treatment for leukaemia. There are also a number of new regenerative therapies that are being used to help patients in the clinic. For example, there are skin regeneration treatments for burns patients and people with diabetic ulcers, treatments for anaemia and cartilage damage, and new options for reconstructive surgery.
Work is now underway to develop potential future treatments. One approach is looking at whether transplanting adult cells can stimulate damaged tissue to repair itself. Stuart Forbes, at the MRC Centre for Regenerative Medicine in Edinburgh, is investigating how cells called macrophages, which are extracted from patients’ bone marrow, can be used to encourage damaged liver cells to repair themselves. Another MRC-funded clinical trial has shown how this type of cell therapy can stimulate the self-repair of nerve cells, restoring limb movement in dogs that have injured their spines. Efforts are now focused on how to use this technique to help human patients.
In a second approach, researchers are transplanting specific cell types or tissue grown in the lab to actively repair damage. This is where the use of pluripotent stem cells – in particular, human embryonic stem cells (hESC) – has the most potential. The first hESC-based clinical trial has just started in the UK to treat the juvenile eye condition, Stargardt’s macular dystrophy. Another trial, led by Professor Pete Coffey at University College London, will test the use of hESC to treat age-related macular degeneration. This is a degenerative condition leading to blindness which affects around 1 in 4 people over the age of 60 in the UK.
MRC scientists are also using hESCs in other disease areas. Tilo Kunath, at the University of Edinburgh, is creating dopamine-releasing brain cells from hESCs that can be used as potential cell ‘transplants’ to treat patients with Parkinson’s Disease. And at the University of Sheffield, Marcelo Rivolta is exploring new ways of treating congenital deafness, which affects 1 in every 1,000 children, by replacing the sensory hair cells in the inner ear. Marcelo’s team has shown that these cells, when grown from hESCs, can be transplanted to restore hearing in gerbils. They are now looking to develop this approach into a treatment for humans.
How is the MRC involved?
MRC activity in regenerative medicine
Promoting stem cell research and regenerative medicine is a priority for the MRC. We have supported pioneering stem cell research since the field first emerged, and remain at the forefront of regenerative medicine. In the 1980s we funded Sir Martin Evans’ Nobel Prize-winning work to isolate and genetically manipulate embryonic stem cells for the first time, and today our scientists are investigating the use of stem cells to treat blindness, heart disease and neurodegenerative diseases such as Parkinson’s disease and Multiple Sclerosis.
We are the main funder of regenerative medicine research in the UK, and spend in the region of £40 million per year in this area. Our work is guided by a Strategy for UK Regenerative Medicine (PDF, 1.60MB) which describes the many opportunities and challenges faced by the field. As well as supporting individual teams of scientists, we have invested in MRC research centres, units and institutes across the UK such as those in Edinburgh, London, Oxford and Cambridge.
Working together to tackle obstacles
The field of regenerative medicine faces many technical and scientific challenges. These include understanding how to turn stem cells into the type of cell needed and how to manufacture them safely and in large-enough quantities for use in the clinic. It is also crucial to figure out how to target treatments to the part of the body that needs repairing, and to find ways of stopping the body from rejecting transplants.
To tackle these and other obstacles, we helped to launch the UK Regenerative Medicine Platform (UKRMP) in 2013, together with BBSRC and EPSRC. This £25 million initiative has brought together leading research teams from different universities and different areas of science such as biology, medicine and engineering. This will help to ensure that promising scientific discoveries in regenerative medicine are translated into the clinic where they can benefit patients. The UKRMP will work closely with the newly established Innovate UK's Cell Therapy Catapult, which promotes the commercialisation and late-stage development of regenerative medicine products, as well as with research charities and other stakeholders.
It is important that researchers can access and use human stem cells that are ethically-sourced and reliable. We play a leading role in this area by making sure that UK human embryonic stem cell (hESC) research is appropriately regulated. Our activity includes MRC funding for the UK Stem Cell Bank – the world’s first – which provides ethical and high-quality hESC lines that scientists in the UK and overseas can use for laboratory and clinical work. These hESC lines must be produced to the highest quality in order to be used in patient studies. To help with this, we have funded three centres to produce more than 20 hESC lines that are now being used in clinical studies (see ‘From the lab to the clinic’).
As well as the UK Stem Cell Bank, we established the Human Induced Pluripotent Stem Cell Initiative (HIPSCI) in 2013, together with Wellcome Trust. HIPSCI is creating a catalogue of iPS cells from over 500 healthy volunteers and 500 patients with genetic disease. These cells will be made available to scientists who want to do laboratory research on the effects of our genes on health and disease. Their work will help us to understand how iPS cells can be controlled and used in future stem cell therapies.
Our work in regenerative medicine is not limited just to the UK. In the past three years, we have collaborated with the US and China on stem cell research. Together with the Californian Institute of Regenerative Medicine in the US, we are addressing new approaches for treating age-related macular degeneration and acute myeloid leukaemia. We are also working with the National Natural Science Foundation of China on a number of projects that link the best UK and Chinese labs in stem cell research.
Our membership in the International Stem Cell Funders Forum (ISCF), which brings together the world’s major biomedical funding organisations, has allowed us to take a leading role in encouraging international working, sharing resources, and helping to establish best practice among researchers. An example of this is the International Stem Cell Initiative (ISCI) project, led by Professor Peter Andrews at the University of Sheffield Centre. ISCI was set up to shed light on the factors that influence stem cell growth and behaviour. It does this by bringing together labs from across the globe to share data and resources. Work by ISCI has helped to identify unstable regions within the chromosomes of pluripotent stem cell lines, which need to be controlled if the lines are to be used as therapies in the future.