Turning Lead into Gold: the Philosopher’s Stone of Cell Biology

iPS cells – a potential cure-all, or are we caught up in the hype?

The evolving world of cell biology has put forward many a proposed miracle cure in recent years. First came the advent of monoclonal antibodies, ready and set to target and kill all forms of cancer under the sun; then came gene therapy, a cure-all for genetic diseases such as cystic fibrosis and even red-green colour blindness. If you’re thinking this all sounds too good to be true, well you’re right; the buzz around both of these technologies has died down somewhat because they have large, perhaps insurmountable issues when it comes to applying them to actually treating disease.

The newest craze in the world of disease-curing technology is, you guessed it, stem cells. They’ve been around for years, but now they’re emerging in a new form – induced pluripotent stem cells, or iPS cells. IPS cells are pluripotent stem cells – they can turn into any cell present in the adult body – that have been made by turning a fully differentiated adult cell into an undifferentiated stem cell that can divide to produce more stem cells which can then be turned into anything. They were developed by Shinya Yamanaka of Kyoto University, who recently won the Nobel Prize for this discovery. He produced them by taking some of the genes that are active in stem cells and putting them into another type of cell, a skin cell for example. A combination of four of these special stem cell genes reprograms the skin cell so it becomes something that looks and acts like an embryonic stem cell (cells taken from very early embryos that produce all cells of the body).

On paper this looks like a major breakthrough which will cure all ills; stem cells were the previous miracle cure for everything, and are still being worked on now to try to grow replacement nerves for rats with spinal damage (of course they hope it’ll work in humans in the future…), and recently to grow a replacement trachea for a woman who would otherwise have died. IPS cells have a certain home-field advantage over other types of stem cells; you could potentially grow them from the patient’s own cells, and then implant them with absolutely no risk that their body will reject them. Embryonic stem cells, as the name suggests, come from developing embryos, so they aren’t similar enough to the patient’s own cells that they won’t reject them. Of course, taking cells from a poor unsuspecting human embryo to grow a new heart in the lab isn’t really allowed and is in fact legislated against, and this is where the other advantage of iPS cells comes in – you can obtain them from live donors or even the patient themselves, as long as they consent – there are no legal or ethical guidelines to stop them from being used in research. In clinical applications, however, iPS cells may be subject to different regulations than embryonic stem cells but they may in fact face more substantial regulatory challenges due to the methods in which they are made.

At this point iPS cells may still sound like a peachy idea, but there are a few complications that threaten to hinder or even halt development of the clinical treatments that look so promising. Firstly, all of the four genes that are used to produce iPS cells have been implicated in producing various forms of cancer and iPS cells are actually similar to cancer cells in many ways. In some studies in which iPS cells were implanted into mice, they developed tumours. Imagine the devastation and uproar if a patient who put all their faith in being cured by a revolutionary new treatment were to end up in a worse position because of it. Such an incident would likely dry up any funding for developing clinical treatments, which have so much potential – it was claimed that iPS cells have already been used clinically (although this turned out to be nothing more than a lie from a fame-hungry scientist), but to prevent a disaster like this from occurring we should wait until such potentialities have been ruled out.

Although iPS cells look and act like embryonic stem cells, there’s lots of evidence to show that they’re really quite different; in any specialised cell – a liver cell for example – its DNA has various modifications done to it that help differentiate it from other cell types. When the four genes are added to wipe the cell’s memory and reprogram it into a stem cell, some modifications won’t be fully wiped out and the DNA modification pattern looks nothing like a stem cell. We have no idea what this would actually do in the long term, but it might be an issue if you’re trying to turn your newly made iPS cells into a heart cell while it still remembers being a liver cell.

When you’re seriously ill, you would like to receive the best treatment as quickly as possible. IPS cells are not a quick fix; in fact they may take up to 6 months to make, validate and differentiate the a patient’s cells into those they require for treatment. It wouldn’t be a cheap option either; it’s been estimated that producing a batch of iPS cells and processing them for the treatment of one patient could cost in the region of 100,000.

We may overcome the technical issues associated with making and using iPS cells to treat disease, but it will be a long road ahead, and we might just not make it, yet they have great potential in other areas too. IPS cells can be reprogrammed to produce a particular cell type affected by a certain disease, and then used to test the effectiveness of new drugs. I believe that drug trials will be the future of iPS cells, but I’d also like to cure every disease under the sun, so I remain optimistic. Keep your eyes peeled for the most fashionable cell in biology, but don’t expect a miracle just yet.

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