“PLURIPOTENT” is a long word that means “able to do many things”. It is the technical term applied to stem cells that can generate many different sorts of bodily tissue, rather than just one sort, which is all that lesser stem cells can manage. But many researchers hope these cells will be pluripotent in other ways, too. Not only might they be used to make replacement tissues and organs for transplantation into those whose existing body parts no longer work properly (an approach known as regenerative medicine), they might also be used to produce pure cultures of cells for the early testing of drugs.
The culturing and use of human pluripotent stem cells is controversial because the natural source of such cells is embryos, which are destroyed by the process of extraction. But in 2007 two groups of researchers, one in Japan and the other in America, announced that they had worked out how to make adult skin cells behave like natural pluripotent cells, by adding four activated genes to them. The result is known as an induced pluripotent stem (iPS) cell.
On January 3rd AstraZeneca, a British drug company, said it would buy human heart muscle, blood vessels, nerve cells and liver cells made from iPS cells by Cellular Dynamics, a company founded by James Thomson. Dr Thomson, a biologist at the University of Wisconsin, is the man who led the team that, in 1998, isolated the first human embryonic stem cells and in 2007 published the American version of the iPS work.
AstraZeneca has two plans for its purchases. One is to use them to find molecules that encourage non-pluripotent stem cells to turn into mature tissue. Such molecules could act as drugs that coax damaged tissue to heal itself. The second is to use iPS cells to test drugs that have nothing to do with regenerative medicine.
Too often, a promising-looking drug fails late on in a clinical trial. Sometimes this is because it does not deliver the promised benefit. Sometimes, however, it works but its side effects prove more dangerous than the disease it is supposed to treat. The cost of failed trials is an important reason why drug research is so expensive. AstraZeneca therefore plans to use Cellular Dynamics’s cells to check the toxicity of potential medicines before they get inside a human being, in order to reduce the number of trials that fail for the second reason.
And AstraZeneca is not the only company using iPS cells in new ways. In December GlaxoSmithKline, another British firm, described an experiment in which it assaulted neurons derived from iPS cells with beta-amyloid, a molecule linked to Alzheimer’s disease, and then tested whether the beta-amyloid responded to hundreds of existing drugs. The findings of this experiment will be published in Stem Cell Research in March.
Another trick made possible by iPS cells is to derive them from patients with specific ailments—particularly aliments with a genetic component—and then nudge the induced cells into becoming the type of cell afflicted by that ailment. Several groups of researchers have used disease-prone cells created in this way to explore how the disease in question develops, and whether it succumbs to drugs.
George Daley, of Harvard University, is one of the most enthusiastic explorers of these “disease in a dish” models. In 2008 he created stem-cell lines from people with ten different conditions, including Down’s syndrome, juvenile diabetes and Parkinson’s disease.
Such models are hardly foolproof—Dr Daley himself acknowledges that the technology is still in its infancy—but eventually they may bring new drugs. iPierian, a company that Dr Daley helped found, has used iPS cells to develop two antibodies that might be used to attack tau, a protein implicated in Alzheimer’s disease, and also to clear up inflammation linked with Alzheimer’s and other neurodegenerative conditions. That is a use far removed from the original idea of employing stem cells in regenerative medicine. The plurality of their potency, then, is only just beginning to be explored.
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