Embryonic stem cell research and therapy
Embryonic stem cells are derived from early embryos and have the ability to differentiate into any cell type. A renewable, tissue culture source of human cells capable of differentiating into a wide variety of cell types would have broad applications in basic research and therapeutic techniques.
In his original report, Thompson demonstrated that human embryonic stem cells could be coaxed into developing gut-like structures, bone, cartilage and muscle (1). Scientists anticipate that in the future stem cell lines will provide a virtually unending supply of pancreatic cells for diabetic patients, neuronal cells for patients with neural disorders such as Parkinson’s or Alzheimer’s disease, and a host of heart cells that may treat a variety of cardiac problems.
Dr Thomas Okarma, who heads up the Geron Corporation, claims to have heart cells that ‘beat’ in laboratory dishes developed from stem cells (2). If it can be produced in sufficient quantity this source of ‘normal’ human tissue could be of major importance to the pharmaceutical industry for drug screening. Current screening of potential new drugs is done using cell lines derived from animals or ‘abnormal’ human tissue such as tumor cells. But using tissue that is different from the ultimate target means that certain side effects and potential benefits are sometimes missed.
A more exciting and pressing use of this tissue, however, will come in the form of dramatically improving transplant medicine. Currently, the wait for transplant from cadavers is long, with many patients dying while waiting (3). Some receive an organ only to have it rejected by their own immune system or to die from infection because of immune suppression. Not only might stem cell technology obviate the need for cadaver donation – it could also resolve the problem of rejection.
Banking of multiple cell lines with varying genetic spectrum that can be matched to patients is one possibility. Alternatively, transgenesis and gene targeting techniques can be used to introduce the patient’s genes into the stem cell line. One of the most promising techniques is what is known as therapeutic cloning. Here, the stem cell line is created using the genetic properties of the prospective recipient via somatic cell nuclear transfer. Blastocytes obtained through nuclear transfers would be used to generate the embryonic stem cells that could be differentiated to specific tissues or organs for transfer to the nuclear donor.
The resulting tissue will be an almost exact genetic match to the patient and will therefore not face rejection and transplantation can be made much safer without the need for immune suppression. Human nuclear cell transfer is legal in the UK, but is liable to become a criminal act in the USA pending an upcoming vote in the Senate.
There are major obstacles to overcome before a stem cell line is liable to reach clinical trials. The exact process of differentiation is not yet understood and although embryonic stem cells can, in principle, provide for all human tissue, scientists are some way from controlling the process. Mouse embryonic stem cells are known to be tumorigenic – that is, they can grow uncontrollably and become cancerous. It is likely that human stem cells will have similar properties. Safeguards, such as suicide genes to destroy implanted tissue, will have to be considered.
Should the use of nuclear transfer ever become widespread there will be an urgent need for human egg donors and it is unlikely that the willing population will be sufficient to meet demand. Alternative use of animal oocytes will need to be considered and the relative risk of human to animal viral transfer tackled (3). Alternatively, research using eggs may point the way to methods which mimic their properties using other human cells and chemical agents.
But there is no reason to believe these problems are insurmountable – and the potential value for human medicine is enormous. It might be expected that the richest nation on Earth would encourage its top scientists to pursue this work with vigor rather than limiting funding opportunities, creating legal barriers and fencing off any newly developed cell lines.
Stuart Derbyshire is an assistant professor in the University of Pittsburgh Department of Anaethesiology. He is a contributor to Animal Experimentation: Good or Bad?, Hodder Murray, 2002 (buy this book from Amazon (UK) or Amazon (USA)).
Stop stemming the research, by Stuart Derbyshire
(1) Thomson JA, et al, ‘Embryonic stem cell lines derived from human blastocytes’, Science 1998; 282: 1145-1147
(2) ‘The promise in selling stem cells’, New York Times, August 26, 2001
(3) Pig organ transplants: you could die waiting, by Stuart Derbyshire
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