Shift in stem cell hopes

Scientists are beginning to see stem cells as research tools to study the mechanisms of disease

Many scientists no longer see cell therapy as the first goal of stem cell research, parting company with those whose near-term expectations for cell therapy remain high. Instead, these researchers envisage a longer-term programme in which human embryonic cells would be a research tool to study the mechanisms of disease. From this, they say, many therapeutic benefits may emerge, like new drugs, which would probably be available at least as soon as any cell therapy treatment.

Thomas M. Jessell, a neurobiologist at Columbia University Medical Center in New York, said he hoped to see the research generate new drugs for neurodegenerative diseases within the next five years but that it could be a long time before rational cell-based therapies are effective. 8220;For the next few years the most rational way forward is not to try to push cell therapies,8221; Dr Jessell said. Scientists have spent the last five years mostly in learning how to grow human embryonic stem cells in the lab and how to make them differentiate.

Dr Ron McKay, a stem cell researcher at the National Institutes of Health, said, 8220;Progress has been mostly incremental, but it is clear that human embryonic stem cells can differentiate8221; to cells of the sort that might be useful in therapy.

Government policy has slowed research with human embryonic stem cells in many ways, scientists say. To work with unapproved lines, government-supported researchers must not only raise private money but also keep their government-financed work separate from their work on unapproved stem cell lines.

The hope of using human embryonic stem cells for cell therapy has been driven in part by the great success of bone marrow transplants, in which a patient8217;s blood supply is regenerated from his own blood-making stem cells. But these cells are different from embryonic cells; they already exist in the adult body. Bone marrow transplants are 8220;a special case, but the general applicability of that to any other disorder is a very big step,8221; Jessell said.

Besides the technical difficulty of growing the precise type of cell needed for cell therapy, researchers face the theoretical problem that new replacement cells are likely to be vulnerable to the same disease that killed the patient8217;s cells in the first place. Ideally, a disease process must be understood and arrested before new cells are introduced.

Many researchers have come to see the primary benefit of human embryonic stem cells as models for human disease. The idea is to take a cell from a patient, convert it to embryonic form, and then make it mature into the type that goes awry in the patient8217;s disease, whether it be a dopamine-producing cell for Parkinson8217;s disease or an insulin-making cell for diabetes.

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Somewhere down this developmental path, the basic cause of the disease may emerge, and be available for study in a dish of cells. The diseased cells should also provide an excellent means of screening thousands of chemicals for new drugs.

8220;Stem cell biology is just a rubric that applies to many things going on in biology,8221; said John D. Gearhart, a Johns Hopkins University stem cell expert. 8220;I personally feel the beauty of these cells is that we8217;ll learn a lot about human biology and disease processes, and that information will be more important than the cells themselves.8221;

Researchers have not, however, abandoned cell therapy, in which cells themselves would be used to regenerate tissue. In Parkinson8217;s disease, for example, dopamine-producing cells from aborted foetuses, when injected into the brains of Parkinson8217;s patients, do have an effect, suggesting that a better source of cell could have therapeutic value. 8220;So it8217;s the perfect place to go in,8221; said Dr Asa Abeliovich of Columbia University Medical Center. Abeliovich said that with Alzheimer8217;s disease, in contrast, 8220;We don8217;t know how or what to replace.8221;

Cell therapy requires making a stem cell develop into a heart or liver cell or whatever tissue needs replacing. It seems some cell types are easier to generate than others. 8220;For some tissues we are doing extremely well, and for others we8217;re really hurting because we don8217;t know enough about the early stages of differentiation,8221; Dr Gearhart said.

NICHOLAS WADE