The dream of regenerating human organs is as old as Prometheus. Chained to his rock, the Titan survived attacks by an eagle that feasted on his liver by growing it anew under cover of darkness. When Mary Shelley wrote Frankenstein, her shocker on the creation of life, she gave it the alternative title The Modern Prometheus.
But myths have a habit of becoming reality, and life of imitating art. For more than a decade we have been seduced by the idea that it may truly be possible to recreate organs. Our response to this possibility incorporates both the Promethean dream and the Frankenstein nightmare, inspiring hope and fear in almost equal measure.
But although talk has been plentiful, progress appears slow. For every advance in the science of stem cells, there has been a retreat. It is plain that unlike, say, the invention of vaccination, this is not going to be a “quick and dirty” victory achieved without a deep scientific understanding. Vaccination worked long before there was any real knowledge of the immune system that made it work. But it does not seem that the stem cell scientists will be so lucky.
Stem cells are the wellsprings of life. Unlike the specialised cells of the skin, the muscle, or the brain, which have narrowly defined functions, stem cells are full of infinite possibilities. They can develop, given the right setting, into any of those specialized cells. In theory, they could replace those lost by age or illness just as Prometheus regenerated his liver. They are “pluripotent”, in the jargon.
The obvious place to find them is in the embryo, the small bundle of cells produced by the fertilisation of egg by sperm that will develop into a human being. In 1981, two teams independently isolated embryonic stem cells from mice and, in 1998, a technique was developed to isolate and grow human stem cells in tissue culture, which were able to create the huge number of cells needed for clinical interventions. The stage appeared set for stem cell treatments to transform medicine.
More than a decade later, a more sober mood prevails. Embryonic stem cells are finally in clinical trials but it has been a long road, both scientifically and politically. Ethical question marks over the morality of using human embryos halted public backing for the research for many years in the US, science’s greatest powerhouse, and diverted attention instead to the idea of transforming adult cells back into a class of cells called induced pluripotent stem cells (iPS cells). By winding the clock back, it is possible for iPS cells to regain the qualities of those present at the beginning of life, and bypass the moral dilemmas.
Cells of this sort were the first to achieve some success. In 2007, mice with sickle cell anaemia were cured by infusing them with iPS cells created from their own skin and modified by gene-splicing techniques so that they no longer contained the sickle-cell gene. It was a brilliant proof of principle, but mice are not men. The technique cannot be used in humans because the genetically-modified viruses used to create the iPS cells could trigger cancer.
Several routes to iPS cells have been tried to get round these difficulties. At first, it seemed that embryonic stem cells could be made by implanting the nucleus of a patient’s adult cell into an unfertilized human egg whose nucleus had been removed – the same technique as cloning. But the method would require hundreds of eggs for each patient. In 2007, Shinya Yamanaka of Kyoto University found that by injecting four protein factors into the adult cell he made it revert to the embryonic state. But these cells appear to retain a memory of their previous identity that denies them pluripotency.
The latest twist came earlier this month when a team from New York Stem Cell Foundation Laboratory led by Dr Dieter Egli announced a new way of making iPS cells using human eggs. Their technique differed because they did not first remove the nucleus of the egg before inserting the adult cell. To their surprise, it worked: an embryo developed to the blastocyst stage, which enabled stem cells to be harvested. But the resultant cells are useless for therapy, because they still contain the extra set of chromosomes from the original egg nucleus. This was, said Robin Lovell-Badge of the National Institute for Medical Research: “An ending that still falls short of the original aim – they did not obtain useful cell lines. However, the work may reveal a way to overcome some problems.”
While iPS therapy has been stalled, more direct approaches to rebuilding the body have achieved some success. In July this year, a man was given the world’s first synthetic windpipe in an operation at the Karolinska University Hospital in Stockholm. Made from a special polymer developed at University College London, it was coated with cells taken from the patient’s bone marrow, which were persuaded to transform themselves into tracheal lining cells. Similar techniques have been used to create artificial urethras and larynxes.
These are not pluripotent stem cells, but clearly possess some ability to adapt to their circumstances. The same is true of the cells taken from fat and bone marrow, which were used recently to treat the injured elbow of baseball player Bartolo Colon, or those used for the hearts of patients who have suffered heart attacks (see box). But what of true embryonic stem cells? The embargo on publicly funded research during the Bush years prevented much progress, but the first clinical trials have finally been launched in the US and Europe.
In September, the UK approved a clinical trial of embryonic stem cells at London’s Moorfields Eye Hospital, using a cell line developed by the US company Advanced Cell Technology. They will be injected into the eyes of a dozen patients with Starguard’s macular dystrophy, a disease that strikes between the age of 10 and 20 and causes progressive vision loss. A similar trial was approved in the US last year, and the first patients were treated in July. Robert Lanza, the company’s chief scientific officer, said: “We’re hoping to prevent the onset of blindness altogether in those patients.” He hopes to launch a second UK trial soon for age-related macular degeneration, a much more common condition.
In the US, another private company, Geron, last year launched a trial of a new cell therapy designed to repair spinal injuries. It uses oligodendrocyte progenitor cells – precursors of nerve cells – that are made from embryonic stem cells. So far, four patients have been treated.
And in Glasgow, a trial of cells to treat stroke was also launched last year, using nerve cells produced by the company ReNeuron. It aims to evaluate the safety of the treatment, and several patients have so far been given low doses.
These are all early-stage trials, designed in the first place to test safety, though hoping also to show some benefits. None has yet to report any results, but at last stem cells have reached the clinic. In the next few years many more trials will be started and we will learn whether the high hopes of stem cell therapy have been realised or whether – like gene therapy, its equally hyped predecessor – it will prove a disappointment.
Fat that heals hearts
Cells extracted from the fat of heart attack patients and injected into the damaged parts of their hearts have shown small but sustained benefits. A trial of 14 patients reported in June that the areas of heart damage were 11% smaller, and the heart’s pumping efficiency 6% greater, in those treated with the cells than those treated with placebo. The improvements had been sustained after the injections ceased, said Dr Henricus Duckers of the Erasmus Medical Centre in Rotterdam.
“This is quite important, because the big thing about cell therapy trials is whether the effect is transient or will be seen on long-term follow-up. We show that if you protect the muscle in the acute phase of a heart attack, you will indeed have sustained improvement.”
The trial used cells called adipose-derived regenerative cells (ADRCs) obtained by liposuction from the patients’ own fat in a process taking about 30 minutes. It takes an hour to separate the AERCs from the fat, using a process developed by Cytori Therapeutics, before they are administered through a fine catheter to the area of damage. The trial continues.Cells extracted from the fat of heart attack patients and injected into the damaged parts of their hearts have shown small but sustained benefits. A trial of 14 patients reported in June that the areas of heart damage were 11% smaller, and the heart’s pumping efficiency 6% greater, in those treated with the cells than those treated with placebo. The improvements had been sustained after the injections ceased, said Dr Henricus Duckers of the Erasmus Medical Centre in Rotterdam.
“This is quite important, because the big thing about cell therapy trials is whether the effect is transient or will be seen on long-term follow-up. We show that if you protect the muscle in the acute phase of a heart attack, you will indeed have sustained improvement.”
Source:
- Nigel Hawkes
- guardian.co.uk, Saturday 29 October 2011
- http://bit.ly/vgv4Pp
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