Embryonic Stem Cells—and Other Stem Cells—Promise to Advance Treatments

Adult stem cells may reach patients first, and induced pluripotent stem cells have greatest potential.

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Thomas Clegg received a heart-failure therapy based on adult stem cells. His heart's performance has improved.

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For Thomas Clegg, the Obama administration's decision in March to lift certain restrictions on government funding of stem cell research was beside the point. The 58-year-old congestive heart failure patient had received an experimental stem cell therapy before the new president even took office. In November, researchers at Methodist DeBakey Heart & Vascular Center in Houston removed some of Clegg's bone marrow and sent it off to a lab, where the best and hardiest of its stem cells were extracted and concentrated. Less than a month after Obama's historic election, those cells were injected directly into Clegg's heart, where the researchers hope they will spark healing and regeneration.

While the attention of the public and ethicists has been focused on embryonic stem cells, research into other kinds of stem cells—including the kind of adult bone-marrow stem cells Clegg received—has been advancing and, in some cases, exploding. "I have never been in a field that is moving at this pace," says Jonathan Chernoff, deputy scientific director at the Fox Chase Cancer Center in Philadelphia. Adult stem cells have been used in bone marrow transplants for 40 years, and trials like the one involving Clegg are expected to expand their use. Meanwhile, many scientists predict that induced pluripotent stem cells, or iPS cells, created by turning back the biological clock of normal adult cells, will one day supplant embryonic stem cells.

But scientists still call embryonic cells the "gold standard" for stem cells, which is why they've been the subject of privately- and state-funded research while federal funds were restricted. It's also why researchers are excited about Obama's move to allow the government to fund research using lines of embryo-derived cells, as long as the embryos are left over from fertility treatments, not created solely for research purposes.

A maturing field. The earliest therapeutic breakthroughs are likely to arise from adult stem cells, which exist in everybody in many subtypes—blood-producing stem cells in the bone marrow, for example, and stem cells in the brain that can become neurons and other brain cells. "In the short term—say, the next five years—most of the therapeutic applications from stem cells will be from adult stem cells," says Steven Stice, director of the Regenerative Bioscience Center at the University of Georgia. Their most likely uses: disorders of the blood and blood vessels, bone, and immune systems, he says.

A host of ongoing projects are testing adult stem cells. In one, researchers at the University of California-San Diego are studying whether stem cells derived from a patient's own fat cells might help treat multiple sclerosis. At UCLA, scientists are looking at using blood stem cells from melanoma patients to create immune cells that recognize and attack their disease. The cells may work in other ways than simply creating new cells to replace diseased ones. In the heart, for example, research suggests they increase blood vessel growth rather than create new heart muscle.

Or, they may lead to new drugs.

"The way stem cells [used as therapy] exert much of their power is to provide the chemical signal to turn on [existing but dormant] stem cells in the body," says Robert Hariri, chief executive officer of Celgene Cellular Therapeutics, which is studying possible treatments based on placental stem cells. So treatments could be derived from those cells, then used to turn on the body's existing stem cells.

But adult cells can be reprogrammed into only a limited number of other cell types, which is where they fall short of more versatile embryonic stem cells. The latter are pluripotent, which means they can become pretty much any type of human tissue. But that comes with problems. "They're the teenagers of stem cells; they have great potential, but we can't always get them to do what we want them to do," says Michael Reardon, chief of cardiac surgery at Methodist.

Guiding their differentiation—their journey to becoming a specialized cell or tissue—with a lab-made brew of growth factors and other chemicals is a big scientific challenge, and it's not the only one. "You want to be sure you can differentiate [the stem cell] into the therapeutic cells," says Judith Gasson, codirector of the Broad Stem Cell Research Center at UCLA. "Once it's differentiated, you have to get it to go to the right physical location in the patient—the nervous system, pancreas, whatever. That's not necessarily going to be trivial." The new cell also has to be integrated into a diseased or damaged tissue, says Martin Pera, director of the Institute for Stem Cell and Regenerative Medicine at the University of Southern California. And how to do that, he says, "is an enormous black box at the moment." Even if scientists can accomplish that, there's no guarantee of a lasting therapeutic effect.