Stemming diseases

September 8, 2000

Foetal cells hold great promise. John Sinden explains an embryonic science

Stem cells are big news. Since the chief medical officer's report recommended that donated human embryos could be used as a source of pluripotent stem cells for medical uses - so-called "therapeutic cloning" - they have repeatedly hit the headlines.

This is due to two remarkable properties that they possess. The first is "self-replication", the capacity to copy themselves to maintain a stock of stem cells; the second is "pluripotency", storing the information to make bone, blood, brain, in fact, every type of cell found in the human body. Although they have yet to be properly tested in animal models, they are seen as a potent source of new tissue. For the first time, products and processes to combat some of the most serious medical needs, including leukaemia, diabetes and heart disease, can be envisaged.

Even as Parliament ponders new legislation to allow the United Kingdom's first research into human embryonic stem cells, the development of cell lines taken from foetal tissue, and therefore outside the ambit of the Human Fertilisation and Embryology Act, has been proceeding at a great pace. Among the leaders in this field is my company, ReNeuron, the only company in the UK developing human neural stem cell products for neurological diseases, including stroke and Parkinson's and Alzheimer's diseases.

These medicines of the future will be cryopreserved, clonal cell lines, regulated as pharmacological drugs and available to neurosurgeons for direct injection into the brain of patients. Scientists have long known that tissue from the foetal brain can integrate after grafting into a damaged adult brain and ameliorate the behavioural deficits seen in, for example, rat models of Parkinson's disease.

For more than 15 years, human sufferers of the disease have been given implants of tissue taken from elective abortions in a series of trials. Following positive reports from individual cases, a 60-patient trial in the United States, sponsored by the National Institutes of Health, recently demonstrated significant benefits from these cell implants over several months in severely disabled Parkinson's patients.

However, the use of primary foetal tissue transplants as a general therapeutic method will be severely restricted. Between four and seven cadavers from first trimester terminations are required to treat a single patient. Therefore, the search for continuous cell lines as alternatives is a priority. The most promising source of therapeutically effective cell lines is cultured neural stem cells, derived from the foetal brain. These are destined to become brain tissue yet they are able to differentiate into all of the different cell types of the brain.

Rodent neural stem cells have been studied in the lab for a while, but only in the past two years have groups in the UK and US reported long-term propagation of the human version. However, all normal human cells have a definite and short life span. The trick we have developed at ReNeuron is to insert a gene into the human stem cells soon after their first cultivation to subvert the normal life span of the cell. This allows the cells to grow under the low temperature culture conditions where the gene is active. But the gene possesses a simple "switch", so that when the cell lines are harvested for implantation and injected into the brain, they become mortal once more as the gene is inactivated at body temperature.

ReNeuron was set up by King's College, London, and Merlin Ventures to exploit research done by its three founders, myself, Jeffrey Gray and Helen Hodges, at the Institute of Psychiatry.

Most of the company's scientists are developing neural stem cell lines using the "conditional immortalisation" approach from a range of foetal brain areas. We have developed a reproducible process and can produce hundreds of continuous cell lines from every tissue sample we receive. With this in mind, we are working towards a first clinical trial in stroke patients before the end of 2001.

John Sinden is research director of ReNeuron Limited. Details: http://www.reneuron.com

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