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FOREWORDSLIFE SCIENCESPHARMACEUTICALSBUSINESS SERVICESEDUCATIONENERGYINFORMATION TECHNOLOGYMANUFACTURINGR&DTECHNOLOGY
REGIONAL DEVELOPMENT
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Chris Mason and Peter Dunnill, Advanced Centre for Biochemical Engineering, University College London, examine the case for integrating regenerative medicine into the NHS sooner rather than later
Today, over one third of a million patients, equivalent to the entire population of Coventry, have already been treated with commercial living cell and tissue-engineered products. These regenerative medicine products are beginning to challenge current medical practice by aiming to cure patients rather than provide pharmaceutical- based symptom relief. This paradigm shift is the medical equivalent of the massive step change that occurred in the lighting industry after Thomas Edison ?perfected? the light bulb.
However, this exciting step change is still in its infancy and will require vision, resources and patience if its great promise of cure for many of today?s untreatable conditions, such as neurodegenerative diseases and heart failure, is to be realised.
The UK has long been recognised as a world leader in the field of stem-cell research with a wealth of outstanding scientists at a number of universities, including: Peter Andrews and Harry Moore (Sheffield); Martin Evans (Cardiff); Roger Pederson, Austin Smith and Azim Surani (Cambridge); and Ian Wilmut (Edinburgh). A number are linked to university spin-out or small biotech companies, such as Axordia, Capsant, Cellcentric, Odontis, Plasticell, Stem Cell Sciences and ReNeuron. The UK is also the undisputed leader in the field of stem-cell banking with the establishment in 2002 of the UK Stem Cell Bank under the leadership of Glyn Stacey. The Bank is collaborating with the international scientific and clinical community to assure the quality of human stem-cell lines used for both research and, in the future, clinical therapy. Thus the first few pieces of the jigsaw are already in place for the UK to build a future healthcare industry sector while creating much-needed advanced therapies to National Health Service (NHS) patients. However, to effectively deliver both ?health and wealth?, the knowledge generated in British academia must be taken up and commercially transformed into real patient therapies by the wealth creators in UK industry.
This essential transition of basic science into commercial development via translational research has been led in the UK by the former Department of Trade and Industry (DTI, now the Department for Business, Enterprise and Regulatory Reform), which has invested in excess of £25m in the sector. For example, via the Technology Programme, the DTI has been active in helping the majority of the start-up ventures that characterise the stemcell and regenerative medicine field so they can work their way through the tough initial years and build links with world-class public sector research groups in the UK.
Chemical drugs have been the basis for great advances in medicine over the past 60 years. They have been supplemented in the last 20 by human therapeutic proteins made in engineered organisms and these are addressing previously intractable conditions, as indicated by rapid growth to a £30bn p.a. global market. However, molecular drugs, life saving though they are, tend to hold the patient in a state of tension with their disease and often with complex side effects.
On the other hand, regenerative medicine offers the prospect of returning tissues and organ to health with a single treatment of living cells rather than multiple doses of a drug sometimes for life. For example, it could provide functioning replacement cells for diabetics, thus freeing them of daily insulin injections, or treat those suffering from Alzheimer?s or Parkinson?s diseases for which there are no long-term satisfactory therapies. At a time when healthcare spending is under increasing strain and yet old-age dependency is set to increase, such a prospect will be worth a lot of effort to bring to fruition.
Achieving success will take determination because living human cells are more complex than molecular medicines and before they are placed in patients their safety must be assured. Fortunately, we are not starting without foundations. Many tens of thousands of leukaemia and lymphoma patients have already benefited from bone marrow transplants as part of routine therapies. Large doses of chemotherapy or radiation are required to destroy the cancer cells. However, these necessarily aggressive therapies not only destroy the abnormal cells, but also stem cells found in the bone marrow that are essential for future blood cell production.
Therefore, donor stem cells or the patient?s own stem cells removed before chemotherapy or highdose radiotherapy treatment are infused after the procedure to repopulate their bone marrow. In a different context, many hundreds of severe burns patients have received life-saving treatment using some of their own skin cells which are removed and multiplied up outside the body. The UK has one of the pioneer companies in this field, CellTran, a spin-out from the University of Sheffield founded by Sheila MacNeil. In some cases of skin damage, such as hard-to-heal leg ulcers that affect 1% of the population at some point, it is possible to use skin cells from a ?non self ? source, which means it can be immediately available: for example the various skin cell therapy products manufactured by Intercytex (Manchester).
In these ways, experience has been built up about issues such as sterile processing and it has established the vital market for relevant commercial equipment and disposables. For example, it has allowed The Automation Partnership (Royston) to apply the robotic systems it has developed for the pharmaceutical sector into versions for regenerative medicine. Furthermore, in the US, where the vast majority of regenerative medicine therapies have been deployed to date, pragmatic regulatory and reimbursement strategies are also being put in place.
While these simpler procedures meet some requirements, the replacement and regeneration needed for more complex conditions demands an even bigger step change. It needs highly defined and often pure human cells to be available in large quantities and at an appropriate cost affordable by the NHS. They must also be specialised if they are to carry out the kinds of functions which become lost in conditions such as diabetes and Parkinson?s disease. It is here that human stem cells, both adult and embryonic, become crucial. We have throughout our bodies (including in the brain) small numbers of stem cells which can come to our rescue by turning into specialist cells that have been lost or damaged. However, sometimes this inbuilt regenerative process requires our intervention.
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A colony of stem cells fluorescently stained against nuclear marker (x400) |
For example, at Moorfields Eye Hospital in London under the direction of Julie Daniels, it is now possible to restore the sight of patients who have had a severe injury to the clear layer at the front of one of their eyes (cornea). If the cornea of a patient has been irreversibly lost due to a chemical burn, a few adult stem cells from the other undamaged eye can be harvested, multiplied outside the body and used to regenerate the matching region of the damaged eye. Presently, this technique has a success rate of about 70%, a huge improvement from before when the only definitive option was to remove the damaged eye as the one means of rendering the patient pain free.
If the regeneration needed is much greater in size there will, however, not be enough adult stem cells and it is here that human embryonic cells have a potential role. Such cells have a capacity for infinite multiplication and can form every specialist cell in the human body (both these characteristics are unique to embryonic stem cells). That means a very small number of human embryonic cells, typically surplus material donated from IVF treatment, can be the basis of many thousands of patient therapies. In time, it may also be possible to ?turn the clock back? on mature human cells to create such invaluable materials without needing embryonic cells. Proof of concept has already been demonstrated by a leading group in Japan working with mice.
The UK, through the Human Fertilisation and Embryology Authority (HFEA), has worked hard to maintain a strict but sensible regulatory framework for the new field and one that acknowledges the delicate ethical issues involved. Use of human tissue and embryos has to be very carefully controlled and clinical studies entail a detailed procedure of obtaining patient consent and explaining the issues. Given this high degree of rigour plus close public consultation at key stages, it is not surprising that the British public is highly supportive. They see only too often in relatives and friends the damage that degenerative diseases in particular can do and for which as yet we lack effective treatment.
To judge how the new field will develop, it is instructive to look back at the beginnings of human protein therapy and particularly of antibody proteins. From the moment in 1975 of the publication of research on a method to produce pure antibodies, later to win a Nobel Prize, it was clear they had enormous medical potential. Compared with most chemical drugs, antibodies have exquisite selectivity in the way they interact with the human system and so promised potent treatment with less side effects. However, the early antibodies were produced as molecules with a large non-human animal component and, though as powerful for therapy as expected, the human body often reacted against their ?foreignness?. It took great courage and persistence from those involved in research and in company R&D to come through the crisis of confidence. They had to resolve not only this scientific problem but also meet the equal challenge of creating safe ways to produce very large. Now this class of medicines is the largest for therapeutic proteins and the fastest growing of any medicine.
We must expect human cell therapy to also follow this switch-back path. There will be early successes and juddering disappointments. This will not be a case of a short burst of venture funding and a brief fanfare of government backing with the box ticked. But, if we follow through from discovery research and underpin the difficult path of translation to practice we will have not only a new and exciting form of medicine, but potentially a major income earner for the UK and one it can defend against overseas competition.
The UK has a strong healthcare system and one that will allow national exchange of clinical data. The necessary NHS information technology is having its problems, but the overall concept is sound. The government is committed to using this capability to encourage healthcare companies to bring more effective new medicines to the UK early in their development, drawn by the coherent study and tracking that will be possible. Foundations are being put in place for molecular medicines and human cell-based therapies will gain from this.
For regenerative medicine, the linkage between clinicians and the bioprocess teams multiplying precious human cells must be closer than is the case for most molecular medicines. The more advanced the procedure the more this will be so. If the NHS is progressive in its adoption of regenerative medicine it will encourage clinicians to be in the international vanguard of adopting the techniques needed and this will also stimulate translational research and the market for local companies. Building on this, UK private healthcare will be able to enhance its already considerable capacity to treat patients from overseas and so generate substantial foreign earnings. The combination of topclass clinical practice and the very sophisticated bioprocessing of human cells is well suited to the UK?s ambitions for a knowledge-led economy.
It has taken approximately 10 years to treat the first third of a million patients with regenerative medicine products. Given the increasing rate of scientific progress and the beginnings of automation in the commercial sector coupled to the unprecedented levels of international political and public support especially in the UK and US, the pace of adoption of the technology into the clinic can only quicken. If the UK is not to be left behind, now is therefore the time to start to integrate regenerative medicine into the NHS, thus potentially improving the nation?s health at the earliest opportunity while increasing the country?s overall wealth by building a successful and sustainable UK commercial sector.
For more information, contact:
Chris Mason MBBS, PhD, FRCS
Stem Cell and Regenerative Medicine
Bioprocessing Unit
Advanced Centre for Biochemical Engineering
University College London
Roberts Building
Torrington Place
London WC1E 7JE
Tel: 020 7679 0140
E-mail: