Stem Cell Research
Each of us starts life as just one cell. This divides many times, eventually to form all the specialised cells that make up our organs and tissues. In some tissues, these cells continue to divide to enable us to grow and to replace damaged cells, but in others the body is unable to produce healthy new cells.
- What are stem cells?
- UK pioneers stem cell research
- Transforming cells
- Stem cell challenges
- Uses for stem cells
- Forward Look in Regenerative Medicine
Stem cells are immature cells that have not yet developed into specialised cells. Found throughout the body from just after conception right through to adulthood, stem cells are able to generate all the different types of cell in our bodies. They may offer a revolutionary way to treat such illnesses like Parkinson’s and Alzheimer’s diseases by replacing damaged body tissues with new cells. The research field is moving very fast as researchers investigate the potential of animal models and human cells in therapies.
In the mid-1800s, scientists realised that cells are the basic building blocks of life. Early last century, European scientists found that all blood cells came from one particular type of ‘stem cell’. For the last 30 years, patients with blood disorders such as leukaemia have been treated with stem cells in bone marrow transplants.
Stem cells from human embryos, fetuses and adults were isolated and grown outside the body in the 1990s. As many diseases are caused by the premature death or malfunction of cells, scientists – including many funded by the MRC – are working on therapies which involve the replacement of damaged cells with stem cells.
In the short term, clinical progress is likely to be made using adult stem cells; for example, for bone and joint repair, heart repair, wound healing and vision research. Stem cells from human embryos can potentially treat a wider range of diseases, many of which are currently incurable. But these therapies will need a longer development time of perhaps between five and 15 years.
The UK plays a leading role in stem cell research, which began when researchers in Cambridge fertilised first animal and then human eggs outside the body1; a discovery that led to the creation of embryos outside the body and the subsequent birth of the first ‘test-tube baby’ (in vitro fertilisation) in 1978. The finding led to a new field of human embryonic stem cell (hESC) research for cell therapy of common disorders, because hESCs could be isolated from embryos for the first time.
Also in Cambridge, in the 1970s, Sir Martin Evans isolated mouse embryonic stem cells2. He showed that cells could be taken directly from a mouse embryo, cultured in a dish outside the mouse’s body, genetically manipulated, and then mixed with normal mouse cells to form an embryo. This allowed the creation of mutant strains of mice that could be used to further medical research.
In 1985, scientists showed that it was possible to turn mouse embryonic stem cells into many different types of blood cell3. US scientists reported in 1999 that they were able to turn hESCs – which could then be cultured in the laboratory – into blood cells4.
Scientists have attempted to transplant fetal nerve cells into the brains of Parkinson’s disease patients to replace damaged brain cells.
Researchers have also suggested that manipulation of adult mouse tissues can turn them into completely different types of cell – such as converting bone marrow cells into nerve or liver cells. Work is in progress to achieve this in humans, but a team has already demonstrated that, in mice, skin cells can be re-programmed to become other cell types5. The new technique involves inserting just four genes into a skin cell. If adapted to humans, a patient’s skin cells could be used to generate new heart, liver or kidney cells outside the body, then returned to the patient and not be rejected by the patient’s immune system.
For stem cells to be useful, they have to be able to do two things: first, renew themselves and, second, change properly into the specific type of cell that is needed.
A stem cell line is a population of identical cells that can replicate themselves for long periods of time outside of the body. In 2003, MRC researchers at King’s College London generated the UK’s first human embryonic cell line, using embryos discarded during the process of preimplantation genetic diagnosis (PGD)6 – which involves the testing of very young embryos for serious genetic disorders. Several hundred hESC lines have now been created worldwide, and, as hESCs have the potential to form nearly all cell types, this could lead to possible therapies for diseases ranging from diabetes to Parkinson’s.
The UK was a world pioneer in setting up a stem cell bank – which supplies high-quality starting materials for the development of stem cell therapy and provides a centralised resource for academics and industry researchers from the UK and abroad. Set up in 2002 and partly funded by the MRC, the bank reduces the requirement for surplus embryos for the development of stem cell lines by individual research groups.
Meanwhile, a huge project that involved analysing in detail nearly 80 hESC lines from around the world has been completed. The International Stem Cell Initiative was commissioned by the International Stem Cell Forum, an organisation that brings together the world’s leading agencies involved in funding stem cell research – including the MRC.
Recently, MRC scientists discovered that embryonic stem cells could develop into the many specialised cells that make up the human body because they keep their genes in a state that is ready for activation at a later stage8. Another team funded by the MRC, in Oxford, has revealed a link between a gene and the activation of human blood stem cells, giving hope that stem cell transplant success for blood cancer patients may be significantly improved9.
Within the next decade, stem cell therapies should begin to emerge as scientific discoveries lead to pre-clinical and clinical tests, addressing a number of distinct diseases.
Researchers are beginning to be able to influence stem cells within the body – for example, cells in the outermost layer of the heart can be guided by a specific protein to move deeper inside and help to repair a failing adult heart. MRC-funded scientists at the UCL Institute of Child Health showed how a certain protein, already known for its ability to reduce muscle cell loss after heart attack, could instruct the heart to heal itself10. In the future, there could be potential for therapies based on patients’ own heart cells.
Scientists are studying how stem cell transplants can treat vision problems and blindness. MRC-funded scientists reported last year that they could replace retinal cells in mice to restore vision11. Teams have begun to grow specific cell types from embryonic stem cells, such as brain cells (neurons), which may treat patients with brain diseases like Alzheimer’s and Parkinson’s, and pancreatic insulin-producing cells, as a potential cure for diabetes.
Bone marrow stem cells, or natural substances from them called ‘growth factors’, may be able to direct repair of the damage done to the brain by a stroke, MRC researchers at the University of Nottingham MRC found. Many patients lose the ability to move after a stroke because nerve cells in the brain die when the oxygen supply is cut off. In a pilot study, the researchers used a drug to release stem cells from the bone marrow in patients who had recently had a stroke. Next, they will explore whether these stem cells are able to travel to the brain and see if they can be directed to repair stroke damage when they get there.
Stem cells are also being used to create models for human disease. MRC scientists have manipulated mouse embryonic stem cells to produce a mouse model for human Down’s syndrome12. They placed almost all of human chromosome 21, extracted from human tissue cells, into the mouse cells, and then used these to generate a mouse that carried this human chromosome.
Stem cells can also be a valuable aid in drug development. Large numbers of a particular type of cell could be grown for use by researchers when testing new therapies, which would be useful for screening potential drugs for toxicity or their impact on a disease. This may also reduce the need for animal testing. Scientists will first need to learn how to control stem cell specialisation very precisely. The MRC is in discussions with pharmaceutical companies about ways to take this forward.
We have also recently begun to learn about the role of stem cells in cancer. Research on stem cells will provide insights into the development of the disease and will offer the hope of new therapeutic targets13.
See also: International Stem Cell Forum
The Research Councils (MRC, BBSRC, EPSRC, ESRC) and Technology Strategy Board have agreed to sponsor a Forward Look in Regenerative Medicine, to produce a coherent set of priorities for regenerative medicine research and development, taking into account current activities, opportunities, and scientific, clinical and commercial relevance. Based on these priorities, and an assessment of barriers to progress, the sponsors will agree realisable plans of action, including priorities for investment (and their justification) and appropriate delivery mechanisms and metrics.
The Forward Look will draw upon the findings of:
- the recently published Government-led regenerative medicine stocktake,
- the findings of a Key Opinion Leaders Workshop, held in September 2011,
- an analysis of the portfolio of sponsor investments in the field, complemented by an overview of other funder activity; and
- an international perspective, based on a review of overseas activity and on comments from overseas experts.
Key Opinion Leaders Workshop
The Key Opinion Leaders Workshop formed a critical part of the Forward Look development, providing an opportunity for the sponsors to hear the regenerative medicine community’s views on research and development priorities.
Attended by over 30 UK experts, drawn from across industry, academia, venture capitalists and the regulatory authorities, the workshop focused on the research and development agenda, as this is the area over which the sponsor group has greatest influence. However, participants were also able to identify barriers and enabling mechanisms in areas beyond the research domain.
Below is the workshop report that captures and ranks the priorities identified by participants over the course of the two-day meeting.
The sponsors, with advice from the cross-Research Council/Technology Strategy Board Regenerative Medicine Advisory Group, are now considering the workshop report alongside the other inputs listed above, to develop a comprehensive strategic plan, for publication in March 2012.
2. Evans (1972). The isolation and properties of a clonal tissue culture strain of pluripotent mouse teratocarcinoma cells. J. Embryol. Exp. Morphol., 28, 163.
3. Doetschman et al. (1985). The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morph., 87, 27.
4. Kaufman et al. (1999). Directed differentiation of human embryonic stem cells into hematopoietic colony forming cells. Blood, 94, 34a.
5. Okita et al. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313.
6. Pickering et al. (2003). Preimplantation genetic diagnosis as a novel source of embryos for stem cell research. Reprod Biomed Online, 7, 353.
7. International Stem Cell Initiative (2007). Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol., 25, 803.
8. Szutorisz et al. (2006). The proteasome restricts permissive transmission at tissue-specific gene loci. Cell, 1375, 127.
9. MacLaren et al, (2006). Retinal repair by transplantation of photoreceptor precursors. Nature, 444, 203.
10. Smart et al. (2007). Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature, 445, 177.
11. Gupta et al. (2007). NOV (CCN3) functions as a regulator of human hematopoietic stem or progenitor cells. Science, 316, 58237
12. O’Doherty et al. (2005). An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science, 309, 2033.
13. Watt et al. (2006). Epidermal stem cells: an update. Curr Opin Genet Dev., 16, 518.