Stem cells STEM CELL SCIENCE IN THE UK. Key facts about research, regulation and funders

Transcription

1 Stem cells STEM CELL SCIENCE IN THE UK Key facts about research, regulation and funders

2 Stem cells THE UK THE PLACE TO BE FOR STEM CELL RESEARCH Stem cell research is one of the most exciting areas of 21st-century science. It offers a potentially revolutionary way to repair diseased and damaged body tissues, replacing them with healthy new cells. A huge amount of research is needed, however, to understand exactly how stem cells work and how their potential can be harnessed for treatments. Stem cells offer hope for common conditions such as Parkinson s disease, diabetes, cancer and Alzheimer s disease, which affect vast numbers of people in the UK and around the world, and for which there are treatments but currently no cures. They are found in a number of places in the human body and occur at the very earliest stages of development through to adulthood. Scientists believe that the most effective way of discovering potential treatments is to undertake research on all types of human stem cells obtained from the various stages of development at which they are found, including very early embryos. All over the world, stem cell research has become the subject of scientific excitement, public curiosity, moral reflection and regulatory challenge. The UK is well positioned, because of its rigorous regulatory regime and its commitment to this research, to identify and realise the therapeutic potential of stem cells. It also has world-class researchers in developmental and reproductive biology and the UK Stem Cell Bank. These strengths present valuable opportunities to influence the international agenda, drive the application of basic research to clinical benefits and attract skilled scientists and international investment in stem cell research. The UK s lead on stem cell research began in the 1970s when scientists at Cambridge University, led by Sir Martin Evans, isolated the mouse embryonic stem cell. Sir Martin, who was supported by the Medical Research Council (MRC) between the 1970s and 1990s, went on to be awarded the Nobel Prize in Physiology or Medicine for Also in Cambridge in the 1970s, Professor Robert Edwards and Dr Patrick Steptoe fertilised first animal and then human eggs outside the body, a discovery that led to the birth of the first test-tube baby through in vitro fertilisation or IVF. It became apparent that moral reflection about the science was urgently required. A committee, chaired by Baroness Warnock, was convened to examine the ethical issues, including whether medical research on human embryos could ever be justified. Their conclusions were embodied in a landmark piece of legislation, the Human Fertilisation and Embryology Act 1990, which allowed scientists to use human embryos for a restricted range of research. Since 2001, this range has explicitly included research into the therapeutic potential of stem cells. Scientists are only allowed to obtain stem cells from very early human embryos that have not developed beyond 14 days and they must demonstrate that the research cannot be done by any other means. A licence to conduct research using embryos must be secured from the Human Fertilisation and Embryology Authority (HFEA). An update of the Act is expected by Autumn continued overleaf...

3 UK Stem Cell Initiative The UK Government set up the UK Stem Cell Initiative in March 2005, with the aim of working with the public and private sector to draw up a ten-year vision for UK stem cell research. Led by Sir John Pattison, the initiative involves representatives from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Department of Health, the UK Stem Cell Foundation, the Academy of Medical Sciences, medical research charities and industry. In late 2005 it reported that the UK is a world leader in stem cell research and development but that more investment is needed if this position is to be maintained. UK Stem Cell Funders Forum The UK Stem Cell Funders Forum was set up in 2006 to take forward the recommendations of the UK Stem Cell Initiative. Its members include research councils, major charities working in stem cell research, UK health departments and the Scottish Executive. The forum allows members to discuss and exchange information on their current stem cell work and funding priorities, to work together to identify barriers to stem cell research and ways to overcome these, and to recognise new areas that could benefit from joint funding. A further part of the forum s remit is to coordinate public communication activities for stem cell research. This has been taken on by the Stem Cell Communication Coalition, a group made up of representatives from the forum s member organisations and from the Royal Society, the UK Stem Cell Bank, the Human Fertilisation and Embryology Authority and the Human Tissue Authority (HTA). Established in 2002, the coalition has coordinated a number of activities including a public survey of attitudes on the use of embryos in medical research. UK National Stem Cell Network The UK Government launched the UK National Stem Cell Network (UKNSCN) in April It is a national body to improve the coordination of stem cell research and the dissemination of research results, in addition to providing a focal point for communication with overseas researchers, the media and the general public. The network s mission is to promote research activities and events at national level which help to speed the translation of basic stem cell research into therapeutic applications in the control of degenerative diseases such as Alzheimer s and Parkinson s, and other conditions such as diabetes. The UKNSCN is funded through contributions from four UK research councils the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the Engineering and Physical Sciences Research Council and the Economic and Social Research Council. Injecting altered cells into early mouse embryos. Vasanta Subramanian, Wellcome Trust

4 Stem cells MILESTONES IN UK STEM CELL RELATED RESEARCH AND REGULATION First IVF baby born after Cambridge scientists fertilise human eggs outside the body. Isolation of mouse embryonic stem cells by Cambridge scientists. Formation of the Warnock Committee to examine the moral questions surrounding assisted reproduction and embryo research. Warnock Report endorses human embryo research into reproductive-related areas but advises tight regulation. Human Fertilisation and Embryology Act passed by both Houses of Parliament. Human Fertilisation and Embryology Authority (HFEA) designated statutory body to enforce provisions of legislation and established in Dolly the sheep is cloned by cell nuclear replacement (CNR) techniques at Roslin Institute in Edinburgh. HFEA and Human Genetics Advisory Commission working party recommends that CNR be investigated for therapeutic purposes but not for reproductive cloning. Report by Donaldson Commission, chaired by the Chief Medical Officer, Sir Liam Donaldson, recommends that research using human embryos (created by IVF or CNR) to increase understanding of human disease and disorders and their cell-based treatments should be permitted subject to controls in the 1990 HFE Act. Also that the research councils should be encouraged to establish a programme of stem cell research and consider the feasibility of establishing collections of stem cells for research use. Human Fertilisation and Embryology (Research Purposes) Regulations designed to implement the recommendations of the Donaldson Commission passed by Parliament; three new purposes added to the 1990 Act. House of Lords appoints a select committee to examine the issues arising from the new regulations, including those of human cloning and stem cell research. Parliament introduces additional legislation prohibiting reproductive cloning. A House of Lords select committee concludes that stem cells have great therapeutic potential and that research should be conducted on both adult and embryonic stem cells. Also that a stem cell bank should be established and overseen by a steering committee. The UK Stem Cell Bank, funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council established at the National Institute for Biological Standards and Control. The bank to be a repository for stem cells derived from adult, foetal and embryonic tissues and to be open to academics and industrialists from the UK and abroad. Steering committee established to oversee the bank and the use of stem cell lines and to develop codes of practice. Researchers at King s College London generate the UK s first embryonic stem cell line. The International Stem Cell Forum (ISCF) made up of 21 funders of stem cell research from around the world including the MRC is established to encourage international collaboration and funding support for stem cell research. continued overleaf...

5 First stem cell lines deposited in UK Stem Cell Bank by scientists from King s College London and the Centre for Life in Newcastle. The ISCF starts a review of global ethics and regulation relating to stem cell research. The UK Government sets up the UK Stem Cell Initiative, with the aim of working with the public and private sectors to draw up a ten-year vision for UK stem cell research. The Hinxton Group, a consortium of 60 researchers, ethicists, scientific journal editors and lawyers from 14 countries, reaches a consensus on a set of international guidelines for stem cell research, which they hope will simplify existing rules and aid collaboration. On behalf of the ISCF, the Australian National Health and Medical Research Council produces a report on intellectual property rights related to stem cell research across the world. It will be key in encouraging further research and development worldwide. American scientists find out how to make stem cells from embryos without destroying the embryo in the process an advance that could overturn ethical objections. The Biotechnology and Biological Sciences Research Council leads the research councils and relevant government departments in establishing a UK National Stem Cell Network to encourage links between researchers and to encourage development of an integrated national stem cell research community. The EU Tissues and Cells Directives became UK law via the Human Tissue (Quality and Safety for Human Application) Regulations Under the Regulations the Human Tissue Authority regulates the procurement, processing, testing, storage, distribution and import/export of tissues and cells for human application. The International Stem Cell Forum publishes the results of a study characterising 59 stem cell lines. The research will help to ensure that future advances in stem cell research involve internationally coordinated quality standards. Teams of researchers at Cambridge and Oxford universities independently discover a new type of stem cell in mice and rats that is very similar to human embryonic stem cells. Two independent teams of researchers at Wisconsin and Kyoto universities produce human induced pluripotent stem cells. These are thought to be very similar, if not identical, to embryonic stem cells but are made by reprogramming an adult (nonpluripotent) cell. The Hinxton Group meets for a second time and produces a consensus statement on pluripotent stem cell-derived gametes, which discusses social and ethical issues and makes recommendations about policy and practice. Human Fertilisation and Embryology bill updated to allow use of hybrid embryos in research.

6 Stem cells THE SCIENCE OF STEM CELLS Stem cells, whether they are derived from an early embryo, a foetus or an adult, have two key properties. Firstly, they have the ability to reproduce almost indefinitely and, secondly, they can be directed to generate the specialised cells that make up the tissues and organs of the body. They have exciting potential for the generation of therapies for repair and replacement of damaged and diseased tissues and organs, as models for the testing of new drugs and helping us to understand at a cellular level what goes wrong in many conditions. Embryonic stem cells A fertilised egg (produced when an egg is penetrated by a sperm cell) is in essence a one-cell embryo. Up until about the eight-cell stage, this very early embryo has the capacity to develop into every cell needed for full human development as well as tissues such as the placenta and umbilical cord. After about five days of development, the embryo consists of a ball of 50 to 100 cells called a blastocyst, which is about the size of a full stop on this page. It is from an inner cell mass within this ball that the embryonic stem cell or ES cell is derived. The cells that comprise it have no fixed destiny at this stage, there is no trace of any structure such as a nervous system which could, for example, produce sensations of pain. Although ES cells can be manipulated to generate all the cell types in our bodies, they cannot develop into a complete embryo on their own. The main source of embryonic stem cells is from surplus embryos donated by couples undergoing in vitro fertilisation (IVF). These would otherwise be destroyed. Developed in the 1970s, IVF is used to treat couples who are having difficulty becoming pregnant. Usually, the woman takes fertility drugs to help her produce more eggs, and these eggs are harvested and fertilised with the man s sperm in the laboratory. The woman is then given hormone drugs before the fertilised eggs are implanted into her womb. Adult stem cells Adult stem cells are found, for example, in human bone marrow, blood, the eye, the brain and skeletal muscle. Their purpose is to replace and replenish cells with specialised functions, such as blood cells. Bone marrow transplants are an existing model of adult stem cell therapy. continued overleaf... STEM CELLS sperm adult stem cells egg fertilised egg totipotent cells blastocyst embryonic stem cells bone tissue neurons blood cells FERTILISATION STIMULATED TO DEVELOP FIVE DAYS GROWTH DIFFERENTIATION INTO ADULT STEM CELLS SPECIALISATION INTO FINAL CELL TYPES

7 For nearly 40 years, patients with blood disorders such as leukaemia have been treated by introducing haematopoietic stem cells via bone marrow transplants. This has been possible because haematopoietic stem cells are readily accessible, unlike many other adult stem cell types found in our bodies, and they are able to replenish blood cells continuously at high rates. Adult stem cells do not appear to have the same capabilities as ES cells. However, under laboratory conditions, some scientists claim to have been able to manipulate them to form other cell types. So it may be possible, eventually, to direct these cells to function in other areas of the body and to repopulate body tissues that have been damaged or diseased. In 2006, researchers found a way to reprogramme mouse skin cells and turn them back into cells very similar to embryonic stem cells. A major breakthrough was achieved in 2007 when researchers also achieved this in human cells, opening up a possible new source of pluripotent stem cells, but without the need to use actual embryos. This technology is at a very early stage and the techniques used to provide the necessary reprogramming require genetic modification and cannot currently be used to develop therapies. Nevertheless, scientists anticipate making rapid progress towards better understanding and refining approaches to generate these cells. The short-term goal is to use them to help model human diseases in the laboratory. The challenge for stem cell research As the one-cell embryo develops, cell differentiation occurs. Differentiation is the increasing specialisation of cells: more specialised cells develop from less specialised cell types. Since most of our body cells have the same genes, differentiation must involve switching on (expressing) or switching off (repressing) different subsets of genes in individual cells. ES cells grown in the laboratory preserve the power to become any cell in the human body. Their destiny is to differentiate. They are infinitely malleable and one of the challenges for scientists is to direct this process. A crucial task for tapping into the therapeutic potential for stem cells is to teach them how to become, for example, muscle cells for damaged hearts or neurons for damaged brains. Another is to ensure they do not continue to grow in an undifferentiated way and in effect turn into a cancer. Much basic scientific research needs to be undertaken in order to understand these processes. The adult stem cells in our bodies replenish cells and tissue in their particular location and, in general, appear to be less malleable than ES cells. However, recent experiments have shown they do have the potential to do a lot more than previously suspected. Stem cells from bone marrow have been induced to differentiate into brain and kidney cells. How this happens is not precisely understood. Research is continuing to explore the mechanism of such transformation and to ascertain whether it is possible to direct adult stem cell differentiation to produce cells for therapies. Cell nuclear replacement Scientists are also exploring a technique called cell nuclear replacement which might potentially provide cells for therapies. In 1996, scientists at the Roslin Institute in Edinburgh produced Dolly the sheep from a mammary cell of a six-yearold sheep. The nucleus of this cell was inserted into a sheep egg cell after the egg s own nucleus had been removed. This process is known as cell nuclear replacement. Factors in the egg (the cytoplasm) reprogrammed the nucleus of the mammary cell and, in a sense, made it forget its original destiny. Instead, the nucleus behaved as if it were inside a onecell embryo. The egg was then implanted into a sheep s womb. This is reproductive cloning. It is illegal in the UK to carry out reproductive cloning in humans. It may be possible, however, to use cell nuclear replacement techniques for human therapeutic cloning. Although the initial steps in both reproductive and therapeutic cloning are the same, subsequent steps and the underlying purpose could not be more different. In therapeutic cloning, also known as somatic cell nuclear transfer (SCNT), the nucleus of an adult cell, for example a skin cell, from a patient with a condition such as Parkinson s, would be inserted into a human egg whose own nucleus had been removed. When the cloned embryo reached the blastocyst stage, ES cells would be derived from the inner cell mass. These cells would be grown in the laboratory and induced to differentiate into the precise cells needed, for example dopamine-producing neurons, which are lacking in the brains of people with Parkinson s disease. Although much research still needs to be undertaken, this form of stem cell therapy could provide new cells, likely to be genetically identical to the patient, with a greatly reduced risk of rejection, a common problem in any form of transplant operation. However, even if this technology is successful, such personalised medicines would be very costly. If the patient suffers from a genetic disease, their cells would also contain the genetic defect, and the resulting ES cells would not be used for cell-based therapy. However, the ES cells could be used to study the disease in the laboratory to perhaps find other types of therapy. Some ES cells are derived from embryos that have failed the process of preimplantation genetic diagnosis (PGD) which involves genetically testing an embryo in a laboratory. Some of these will carry the genetic defect, such as cystic fibrosis, allowing the disease to be studied in the laboratory. Scientists are exploring the possibility of creating embryos, by using human sperm to fertilise an animal egg (hybrid), or transferring the nuclei of human cells into animal eggs that have had almost all their genetic material removed. These so-called human admixed embryos are a type of SCNT. They could provide a plentiful supply of stem cells and get around the shortages of leftover IVF embryos from which stem cells can be harvested or of human eggs that could be used in the same way. In late 2007, the Human Fertilisation and Embryology Authority granted licences to two teams of researchers to create human admixed embryos.

8 Stem cells STEM CELL RESEARCH: REGULATORY ISSUES The Human Fertilisation and Embryology Act of 1990 was enacted to regulate the practice of in vitro fertilisation (IVF) and the creation, use, storage and disposal of embryos produced in this way. It established a regulatory authority, the Human Fertilisation and Embryology Authority (HFEA), which is empowered to approve all embryo research conducted in the UK. Such research is illegal unless it is carried out under a licence granted by the HFEA. In order to receive a licence the applicant must demonstrate that embryo research is necessary and that the proposed research is being done for one of the five purposes specified in the Act: (a) promoting advances in the treatment of infertility; (b) increasing knowledge about the causes of congenital disease; (c) increasing knowledge about the causes of miscarriages; (d) developing more effective techniques for contraception; (e) developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation; or for such other purposes as may be specified in regulations [paragraph 3(2)]. Such other purposes are limited by the language of the Act to projects which increase knowledge about the creation and development of embryos, or about disease, or enable such knowledge to be applied [schedule 2 paragraph 3(3)]. Since the Act was passed, there have been many advances in developmental biology but two stand out: the derivation of human embryonic stem (ES) cells and the cloning of Dolly the sheep in 1996 by cell nuclear replacement (CNR). In response to the cloning of Dolly the sheep, a working party drawn from the HFEA and the Human Genetics Advisory Commission was formed to undertake a public consultation on human cloning. In their report, Cloning: Issues in science and medicine (December 1998), the group recommended that the Secretary of State for Health consider adding two additional purposes for which embryo research could be licensed: the development of therapy for mitochondrial disease and the development of therapeutic treatments for diseased and damaged tissues and organs. Human reproductive cloning was deemed unacceptable. continued overleaf... Egg cell manipulation. Images courtesy of MRC Clinical Science Centre

9 Light micrograph of a human embryo at the two-cell stage of development. Richard G. Rawlins/Custom Medical Stock Photo/ Science Photo Library An expert committee chaired by Sir Liam Donaldson was then appointed and the group was asked to answer two basic questions: should this new type of research be permitted and, if so, were new regulations required? In its 2000 report, the committee recommended that research on embryos (both surplus embryos left over after IVF and embryos created by CNR) be permitted in order to increase understanding of human disease and disorders, and their cellbased therapies. The Human Fertilisation and Embryology (Research Purposes) Regulations were brought forward by the government; they were passed by the House of Commons in December 2000 and by the House of Lords in January The regulations added three new purposes to the five in the Act: (a) increasing knowledge about the development of embryos; (b) increasing knowledge about serious disease; (c) enabling such knowledge to be applied in developing treatments for serious disease. The House of Lords Select Committee on Stem Cell Research was appointed on 7 March 2001 to consider and report on the issues connected with human cloning and stem cell research arising from the new regulations. On 27 February 2002, the Committee reported. Among its conclusions was an endorsement of the Department of Health s (DH) proposals to establish the UK Stem Cell Bank, responsible for the custody of stem cell lines, ensuring their purity and provenance, and monitoring their use. The Committee also recommended that as a condition of granting a research licence, the HFEA should require that a sample of any ES cell line generated in the UK in the course of that research be deposited in the bank. The creation of embryos (from which stem cells may be derived) and the subsequent storage of these embryos is regulated by the HFEA. This includes embryos created from in vitro fertilisation and cell nuclear replacement. Research projects which involve derivation of stem cells by the creation of embryos must be licensed and approved by the HFEA. Researchers must prove, to an HFEA licence committee s satisfaction, that the research application fits in with the purposes of the Human Fertilisation and Embryology (HFE) Act 1990 and the HFE Research Regulations 2001 and that it is necessary to use embryos for the research. In addition to the two licences subsequently granted for human admixed embryos, the HFEA has so far granted two licences to study the derivation of human embryonic stem cell lines using nuclear transfer (therapeutic cloning). The first was in 2004 to researchers at the International Centre for Life at the University of Newcastle, who are investigating new treatments for conditions including diabetes, Parkinson s and Alzheimer s disease. The second, in the following year, was to the Roslin Institute in Edinburgh for the study of motor neuron disease. The regulation of stem cells in the UK is affected by two pieces of legislation: the Human Tissue Act 2004 and the Human Tissue (Quality and Safety for Human Application) Regulations 2007, which fully implement the EU Tissues and Cells Directives (EUTCD). The Human Tissue Act 2004 regulates the removal, storage and use of human bodies, organs, tissue and cells for a number of purposes, including research. The EUTCD which was brought fully into force in 2007 creates a common framework that ensures high standards in the procurement, testing, processing, storage, distribution and import/export of tissues and cells across the EU. The primary aim of the Directive is to ensure the quality, safety and traceability of tissue and cells used for human application. It also aims to support the exchange of tissues and cells between member states.

10 Stem cells INTERNATIONAL ARENA Globally, stem cell research is becoming increasingly competitive. Many countries, such as the ones listed below, are progressing considerably in the stem cell research field, due to increasing funding and permissive regulations. In Asia, Japan has invested heavily in stem cell research and Japanese researchers have been responsible for some important recent discoveries. The Chinese government supports all forms of stem cell research and Chinese researchers are carrying out work of international standing and publishing in European and US journals. Stem cell research is a major priority in Singapore, which has attracted overseas talent with state-of-the-art facilities and generous research funding. The US remains the world leader in stem cell research. Despite restrictions on federal funding for embryonic stem cell research, the US National Institutes of Health (NIH) spends very considerable amounts on other types of stem cell research. Individual US states, such as California, are investing substantially in all forms of stem cell research, including embryonic stem cell research. Canada spends a large amount on stem cell research and the government established the Canadian Stem Cell Network to coordinate research activity and fund major collaborations with a concentration along product development lines. Sweden is a world leader in stem cell research, with a regulatory and ethical environment similar to the UK. Due to its permissive laws on stem cell research, Sweden now leads Scandinavia, and possibly even Europe, in this area. Germany has very tight restrictions that have deterred its scientists from working on embryonic stem cells, but it is a world leader in adult stem cell research. Regulation Regulation of stem cell research varies enormously between different countries. Some countries have no legislation at all, and others ban all such research. Some countries have adopted laws that allow embryonic stem cell research, including therapeutic cloning and the creation of embryos specially for research purposes. A large number of countries have adopted compromise policies, permitting some types of embryonic stem cell research and restricting others. The US has no national laws or regulations to control embryonic stem cell research. However, individual states have introduced their own laws. Some states, such as Florida and Pennsylvania have prohibited embryonic stem cell research. Other states, such as California and Massachussetts, have permissive laws. continued overleaf...

11 Countries with permissive regulation include the UK as well as Australia, Belgium, China, India, Israel, Japan, Singapore, South Korea and Sweden. Although the UK s regulations for embryonic stem cell science are permissive, the system for enforcing them is very strict, more so than in many other countries. Other countries are less permissive. Such countries allow embryonic stem cell research using embryos left over after IVF treatment but may not allow cloning or the creation of embryos specially for research purposes. These countries include Canada, Denmark, France, the Netherlands, New Zealand, Portugal, Spain and Switzerland. There are also a number of countries with tight restrictions or bans on embryonic stem cell research. Within Europe, countries with such laws include Italy, Lithuania, Poland and Slovakia. Different European countries have very different laws on stem cell research. The European Commission will not fund activities that destroy the human embryo, but may fund other research on embryonic stem cells, provided that this research is permissible under the laws of the country where the research is taking place. There have been a number of attempts to create international rules for stem cell research. For example, the International Societies for Stem Cell Research (ISSCR) has drawn up ethical guidelines for the embryonic stem cell research. These guidelines are voluntary, but scientists are coming under pressure from international journals and funding bodies to prove that their research is being conducted in an ethical manner. In 2005, the United Nations General Assembly adopted a declaration calling on countries to ban all forms of human cloning, including cloning for research purposes. However, the declaration is non-binding and has no legal status. The International Stem Cell Forum The Medical Research Council (MRC) launched the International Stem Cell Forum (ISCF) in 2003 along with eight other international funding agencies with similar scientific principles and resources. These agencies all shared the MRC s concerns about the need to create standardised global criteria for creating, storing and maintaining stem cell lines. Today, the ISCF has a total of 21 member organisations in 19 countries. The forum is working on the International Stem Cell Initiative (ISCI). Led by Professor Peter Andrews of the University of Sheffield Centre for Stem Cell Biology, the ISCI has been developing an internationally-agreed set of rules for growing and analysing human embryonic stem cells. The ISCF published a paper in Nature Biotechnology in June 2007 analysing in detail 59 human embryonic stem cell lines. This international collaborative project is now progressing with US$2million of funding. On behalf of the forum, the Australian National Health and the Medical Research Council have developed a document about intellectual property in stem cell science. It covers the criteria for patenting stem cells throughout the world, identifying techniques that may be subject to patenting, highlights patents already in existence and explains how countries are attempting to ensure ongoing access to stem cell resources. Led by Canada, the ISCF is also working on a global review of ethics and regulation of stem cell research, which is being carried out by its Ethics Working Party. The group includes ethicists, research scientists, clinicians and lawyers from the forum s members. Together they are reviewing the different ethical issues and regulations in countries that fund stem cell science, with a particular emphasis on research involving embryonic stem cells. The group aims to draft best practice guidelines for stem cell research and to develop a global register of clinical trials involving stem cells.

12 Stem cells UK COMMERCIALISATION OF STEM CELL RESEARCH Although the commercial, nontherapeutic use of stem cells is already an established part of the process of drug discovery, the commercial and medical benefits from stem cell therapies are still some way off, with the exception of bone marrow stem cell transplants for blood disease such as leukaemia which have been used for many years. The delay in further treatments is partly due to the stringent tests for safety, quality and efficacy required for these therapies prior to their approval for market by the regulatory agency - the European Agency for the Evaluation of Medicinal Products (EMEA). These pre-clinical and clinical studies will typically take a number of years to complete. It is likely that therapies using adult stem cells will emerge first, with embryonic stem cell therapies following later. Despite this, several UK public and private stem cell research companies have been established, such as ReNeuron, Stem Cell Sciences, Axordia and NovaThera. UK stem cell companies are working on therapies for conditions such as stroke, Parkinson s disease, diabetes, cardiac disease and retinal damage of the eye. Some are also marketing their stem cells as drug discovery tools for screening applications in drug development, for example to test metabolism, and in safety tests. Support for commercialisation The UK Stem Cell Bank, which provides a repository for stem cell lines derived from adult, foetal and embryonic tissues, will be a vital resource to company researchers. The bank is collaborating with commercial partners to achieve cell lines of sufficient stability for use by companies. continued overleaf... Blastocyst. Wellcome Trust

13 IVF embryo. Anne Falkner The bank will ensure that cell lines which could ultimately provide the basis for clinical treatment are prepared under Good Manufacturing Practice (GMP), subjected to appropriate safety testing and subsequently handled and stored under quality-controlled conditions. However, some cell lines will require additional tests, which companies themselves may have to carry out. In 2004, the UK Stem Cell Bank set up the first clinical grade GMP facility for human stem cell banking in the European Union. This was followed in January 2006 by the opening of the UK s first GMP laboratory for the derivation of clinical grade human embryonic stem cell lines, at the Medical Research Council s Centre for Stem Cell Biology at Sheffield University. Companies may also benefit from the UK Stem Cell Foundation, which was established in 2005 to support the transfer of stem cell techniques from the laboratory to the clinic. The foundation aims to raise funds from private donations to directly fund projects where research has indicated potential for direct clinical benefit to patients in the short term. As of early 2008, the MRC had approved five joint awards with the foundation, addressing bone and cartilage repair, liver regeneration and brain repair. The UK Government funds stem cell research in companies directly via its Technology Strategy Board. This money is available for collaborative R&D projects in specific areas, including bioscience and healthcare, and is allocated to consortia on a competitive basis. The MRC has developed strategies with the Technology Strategy Board for academic and industry cooperation, and there has already been a joint call in regenerative medicine.

14 The Alzheimer s Society is the UK s leading care and research charity for people with dementia, their families and carers. With more than 250 branches and support groups, it provides information and support for people with any form of dementia and their carers through its publications, helpline, website and local network. It advises professionals, runs quality care services and campaigns for improved health and social care and greater public understanding of dementia. The society funds an innovative programme of biomedical and social research on the causes of, cures for and care for people with the disease. What is Alzheimer s disease? Alzheimer s disease is the most common form of dementia. More than 700,000 people in the UK have dementia, of whom 15,000 are under the age of 65. Dementia affects one in 14 people over the age of 65 and one in six over the age of 80. More than 60 per cent of the people with dementia have Alzheimer s disease a progressive, degenerative disease of the brain, which destroys cells and disrupts transmitters that carry messages in the brain. Stem cell research and Alzheimer s disease In Alzheimer s disease, nerve cells die in a random way, interrupting the complex interconnections of nerve cells in the cortex, which is the outer layer of the brain. It is this network of cells that facilitates our memories, personalities and behaviour patterns. Because of the loss of many different nerve cell types in the brain, and the impact that the disease has on communication between cells, developing therapies for Alzheimer s disease is more complicated and challenging than for some other neurological conditions. Until recently, it was believed that we are born with a certain number of nerve cells and that once these cells die, they cannot be replaced. However, this concept changed after the discovery of a population of brain cells, called neural stem cells (NSCs), which can develop into new nerve cells. Experiments on animals have shown that implanted NSCs can move towards areas of damage and take on a nerve cell-like structure. This has raised hopes that NSCs may be a useful new therapy for illnesses where nerve cells are lost. However, in Alzheimer s disease, the loss of nerve cells is very widespread and there are doubts that the there are sufficient NSCs in the adult brain to be able to compensate for this loss, even if we knew how to stimulate them. Research on NSCs has revealed that there may be an alternative strategy for replacing lost nerve cells. Other parts of the body also produce stem cells. These stem cells seem to have remarkable plasticity that is, with the appropriate chemical trigger, they can turn into many different cell types, including nerve cells. Indeed, researchers have obtained bone marrow stem cells (MSCs) from rats, grown them in cell culture and have turned them into cells that exhibit the characteristics of nerve cells. This is encouraging because bone marrow is a far more accessible source of stem cells than the brain. continued overleaf...

15 ALZHEIMER S SOCIETY ASSOCIATION OF MEDICAL RESEARCH CHARITIES BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BRITISH HEART FOUNDATION CANCER RESEARCH UK DIABETES UK HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY HUMAN TISSUE AUTHORITY MEDICAL RESEARCH COUNCIL PARKINSON S DISEASE SOCIETY THE ROYAL SOCIETY SCOTTISH STEM CELL NETWORK UK STEM CELL BANK WELLCOME TRUST MSCs are also easy to maintain in the laboratory, can be grown easily and can be frozen and stored for long periods of time. The Alzheimer s Society has funded stem cell research since 2002 when it awarded a three-year fellowship. The project involved animal models of nerve cell loss and the replacement of nerve cells with MSCs. Since then, we have awarded two further fellowships and one PhD studentship, and funded a project in understanding how stem cells may be useful in the treatment of dementia. The direct benefits of this work in terms of a possible therapy may not be realised for some years. However, if successful, these projects will indicate whether we may be able to replace dead nerve cells in a widespread and specific manner something that has long been thought impossible. Future prospects The society sponsors research through its Quality Research in Dementia (QRD) programme. The focus of QRD is to fund research that has direct benefits on the quality of life for people with dementia and their carers either through improving care, or by taking us closer to understanding the causes and finding a cure for dementia. A network of 170 lay people with personal experience of dementia is actively involved in setting the research agenda for society, assessing outcomes and guiding the programme. Every application that we seek to support has been prioritised by this consumer network as well as rigorously peerreviewed by leading international academic researchers. Stem cell research has consistently been identified as a priority by the QRD consumer network. The Alzheimer s Society hopes to receive more applications for funding research of this kind. We are delighted to work in collaboration with the MRC and other charities to support this important area of research. Contact Alzheimer s Society Central Office Devon House 58 St Katharine s Way London E1W 1JX Tel: Fax:

16 The Association of Medical Research Charities (AMRC) is a membership organisation of the leading UK charities that fund medical and health research. The AMRC aims to provide effective support and leadership for its members and the wider charity sector involved in medical and health research through the provision of information and guidance and a strong and credible representative voice. It does not conduct or provide funding for medical research, but in this pack you will find examples of stem cell research work supported by several of our member charities. The AMRC produces policy and position statements including on human embryo and stem cell research, and issues regular announcements on these topics, which are available on our website ( We also provide web-based information about stem cell research in our issues in debate section covering: current debate, regulation, legal framework, advisory system and other guidelines, ethical principles, charity perspective (with links to members particularly active in this area), public opinion, patient and carer perspective and further information. Reflecting public opinion a 2007 British Market Research Bureau survey showed that 73 per cent of the UK public support embryonic stem cell research under existing or tighter Government regulation our statement emphasises support for such work within a rigorous regulatory environment, and outlines the potential benefits of this research to the understanding, although not necessarily imminent treatment of a range of conditions. These include heart disease, diabetes, cancer, Parkinson s disease, stroke, arthritis and mental illness. The AMRC has been very active in the debate about modernising the Human Fertilisation and Embryology Bill, in particular the use of human-animal hybrid embryos as a source of stem cells for research. We provided evidence and supported amendments to the Bill in its draft stages and as it progressed through Parliament. In April 2007, the AMRC coordinated a joint letter to the Prime Minister signed by 223 medical research charities and patient organisations, demonstrating a strong stance that the law regulating stem cell research should allow the creation of hybrid embryos. Two such projects were licensed under current law, in January 2008 ( Capitalising on our award-winning partnership with Y Touring Theatre Company ( on Every Breath, a play about the use of animals in medical research, the AMRC is supporting public dialogue on the stem cells debate through a further, similar, partnership. With financial support from the Medical Research Council, Department of Health and AMRC member Action Medical Research, Nobody Lives Forever is a play by highly acclaimed writer Judith Johnson which explores the debate around stem cell research. Y Touring s productions present a range of arguments, and incorporate a live discussion between audience and cast, who stay in role to field questions. Dr Sophie Petit-Zeman, the AMRC s Head of External Relations, is scientific consultant to Y Touring for the project, which tours schools and adult audiences through 2008 and will be the basis for a Mega-Debate project with the Royal Albert Hall, involving 2,000 young people, in spring Dr Petit-Zeman is also a coordinating member of the project s advisory group. contact details overleaf...

17 ALZHEIMER S SOCIETY ASSOCIATION OF MEDICAL RESEARCH CHARITIES BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BRITISH HEART FOUNDATION CANCER RESEARCH UK DIABETES UK HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY HUMAN TISSUE AUTHORITY MEDICAL RESEARCH COUNCIL PARKINSON S DISEASE SOCIETY THE ROYAL SOCIETY SCOTTISH STEM CELL NETWORK UK STEM CELL BANK WELLCOME TRUST Contact Association of Medical Research Charities 61 Gray s Inn Road London WC1X 8TL Tel: Fax:

18 The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK s principal funder of basic and strategic research across the biosciences, much of which leads to advances and applications in the medical, healthcare, agricultural, veterinary and food sectors. It is funded mainly by the Government s Science Budget through the Department of Innovation, Universities and Skills (DIUS). The BBSRC works closely with the other research councils through Research Councils UK (RCUK), and is leading the research councils and relevant government departments in establishing a UK National Stem Cell Network to encourage links between researchers and to encourage development of an integrated national stem cell research community, in response to a report from the UK Stem Cell Initiative in The BBSRC is also leading the research councils in providing focused communications training for UK stem cell scientists. The BBSRC operates a variety of procedures to address ethical and societal issues surrounding the biosciences, including those associated with stem cell research. It supports research on both adult and embryonic stem cells. Our position on stem cell science is published on the BBSRC website: organisation/policies/position/public_ interest/stem_cells.pdf. BBSRC-funded research has led to several commercial developments in stem cell science, including several spinout companies. These include Axordia - novel methods for directed differentiation of stem cells, and RegenTec - selfassembling injectable scaffold for tissue repair. Funding for stem cell research The BBSRC supports pioneering research in the UK on the basic biological properties and behaviour of stem cells from both model organisms and humans. It has played a key role in building up the UK s research capacity in stem cell science, through targeted funding initiatives and specialist training for researchers. Through its response mode funding scheme, the BBSRC supports stem cell research through grants. It also funds the training of stem cell scientists through its Doctoral Training Grants (DTG) to universities. In both of these schemes the areas of study are chosen by the applicants. BBSRC spends at least 9million a year supporting stem cell research and training. It co-funds the UK Stem Cell Bank with the Medical Research Council (MRC). Research The focus of much BBSRC-funded research is on providing more knowledge about how stem cells regulate their ability, as unspecialised cells, to either replicate themselves or turn into particular cell types. This information is essential if it is to be possible to use stem cells safely and effectively in therapies and other biomedical applications. This often involves science that is supported in a complementary way by the BBSRC and the MRC. In 2007, the BBSRC and the MRC started the UK s biggest ever public consultation on stem cell research, funded by the UK Government s Sciencewise scheme. The programme aims to gain an insight into public expectations, aspirations, and concerns about this fast moving and challenging area of science, and includes a national programme of workshops and discussion meetings. Contact Chris St Pourcain, Stem Cell Biology, BBSRC Senior Programme Manager, A poster display on stem cell science, Hope not Hype, produced by the BBSRC and the MRC is accessible at: bbsrc.ac.uk/society/meetings/exhibition_ stem_cells/index.html. contact details overleaf...

19 ALZHEIMER S SOCIETY ASSOCIATION OF MEDICAL RESEARCH CHARITIES BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BRITISH HEART FOUNDATION CANCER RESEARCH UK DIABETES UK HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY HUMAN TISSUE AUTHORITY MEDICAL RESEARCH COUNCIL PARKINSON S DISEASE SOCIETY THE ROYAL SOCIETY SCOTTISH STEM CELL NETWORK UK STEM CELL BANK WELLCOME TRUST Contact Biotechnology and Biological Sciences Research Council Polaris House North Star Avenue Swindon SN2 1UH Tel: Fax:

20 The British Heart Foundation (BHF) is the nation s heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. We rely on public donations of time and money to continue our work. The BHF is the largest independent funder of cardiovascular science in the UK. We make an annual investment in research of around 50 million, and have a research portfolio of around 1,200 studies at any one time. In our view, if appropriate safeguards are in place, bolstered with the stringent ethical guidelines that exist in the UK, stem cell research is appropriate as there are many achievable benefits for heart patients. What is heart and circulatory disease? Cardiovascular disease the term that encompasses all diseases of the heart and circulation kills more than 200,000 people each year in the UK. The main forms are coronary heart disease and stroke, which together cause around three quarters of these deaths. Coronary heart disease is the UK s single biggest killer. It occurs when fatty plaques, known as atherosclerosis, build up in the vital coronary arteries that feed the heart. This can be caused by a combination of environmental, lifestyle and biological factors such as smoking, high blood pressure, or the genes we ve inherited from our parents. The plaques can narrow our coronary arteries, causing chest pain ( angina ) and they can rupture and form a blood clot that completely blocks the artery, causing a heart attack. Thanks to research a significant part of it BHF-funded advances in understanding of the disease have enabled effective treatment and prevention strategies to steadily reduce death rates from heart disease since the 1970s. However, more than 2.6 million people in the UK are now living with heart disease, which can be frightening and debilitating. How might stem cells help people with heart disease? Heart attack can cause loss of heart muscle cells and the development of scar tissue, leading to long-term changes in the heart s size and shape. This can leave people vulnerable to dangerous irregular heart beats and may lead to heart failure, when the heart doesn t pump effectively. Our hearts have a limited ability to repair, so heart damage is usually irreversible. There are currently no treatments to patch up damaged tissue with healthy heart muscle. Stem cell therapy could be part of the solution. We hope that in the future, stem cells could prevent the long-term consequences of heart attack injury by repairing or replacing damaged tissue. We may also be able to use a person s own stem cells to grow heart valves, blood vessels, or even whole hearts for transplant. These replacements would be an exact match to the patient avoiding immune rejection. Our understanding of stem cells is still in its infancy so the BHF is funding research across many aspects of stem cell biology to help us understand this exciting potential therapy. This knowledge will equip us to move forward and give the best chance of success for large studies with patients in the future. continued overleaf...