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Rewriting Life

Stem Cell Hope

Cellular reprogramming could make moot the ethical debate surrounding stem cells.

[To check out a six-minute video featuring two eminent researchers and Technology Review’s editor in chief discussing the hows and whys of embryonic stem-cell research – with spectacular color graphics and images – click here. Note: You can pause the video at any time.]

Embryonic stem (ES) cell research, we hope, will be moving from the laboratory to the clinic in the coming years. The promise of this technology – and the associated scientific challenge – is enormous (see “Stem Cells Reborn”). Worldwide, 17 million people die every year from cardiovascular disease, more than 200 million suffer from diabetes, and millions more fall ill from a wide range of other disorders that may one day be treatable with stem cell thera-pies.

It’s possible that, in addition to generating an unlimited supply of functional replacement cells, ES cell progeny could be used to reconstitute more complex tissues, including blood vessels, bone, and even entire organs such as kidneys or hearts. But even if stem cell researchers learn to generate these various tissues, doctors still will not be able to transplant them into patients without either the risk of immune rejection or the use of immunosuppressive drugs that can lead to a wide variety of serious and potentially life-threatening complications.

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Somatic-cell nuclear transfer (SCNT) – also known as therapeutic cloning – could potentially prevent the immune responses associated with the transplantation of ES cell-derived tissues. Unfortunately, however, using SCNT to treat everyone with cardiovascular disease and diabetes alone would require several billion (yes billion!) human eggs, and at present, it is proving problematic for researchers to obtain even a limited supply of human eggs for research purposes. Of course, aside from the problem of egg supply, there’s also the debate over the ethics of creating – and destroying – hundreds of millions of human embryos to generate patient-specific stem cell lines.

Fortunately, there’s a new area of stem cell research that aims to bypass the need for human eggs and even the creation of embryos. Scientists hope to reprogram patients’ cells in the laboratory so that they enter a stem cell-like state where they have the potential to turn into some (multi-potential) or all (pluripotential) of the 200-plus cell types in the body.

Such advances will hopefully allow us to produce youthful cells and tissues that are genetically compatible with patients. These cellular–reprogramming technologies could become the treatment of choice for chronic diseases. In the same way that the ooplasm of an egg is capable of reverting the nucleus of any cell back to an embryonic state, the cytoplasm of other cell types (such as blood cells) may be capable of reprogramming another cell type (such as a skin cell). This technology has the potential to transform mature body cells extracted from a patient into pluripotent stem cells, while sidestepping the ethical debate associated with both egg cells and embryos.

Unfortunately, it’s unclear whether this goal can be achieved in a few years, or whether it will take decades. To begin with, more research is needed to explain how the egg ooplasm is able to take a fully differentiated nucleus backward in time and turn it into a totipotent cell that has the capacity to generate an entire organism.

There is also tantalizing evidence that ES cells can be used instead of eggs to reprogram somatic cells. Does the magic lie in the cytoplasm or the ES cell nucleus? While you are reading this, dozens of groups worldwide are actively trying to answer this and other questions associated with cellular reprogramming. With a little luck, one of them might get stem cell research out of its ethical bind.

Robert Lanza is vice president of medical and scientific development at Advanced Cell Technology.

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