Science Editor

The combination of Washington and stem cells usually yields more heat than light about the true state of the therapeutic area. But at a recent symposium on "Challenges and Promises of Cell-Based Therapies" held at the National Institutes of Health, a group of eminent researchers proved that even within striking distance of the Beltway, it is possible to get an unpoliticized overview of one of the most controversial areas of research.

James Battey, director of the National Institute on Deafness and Other Communication Disorders, summarized the general feeling by saying that "there's clearly enormous promise for regenerative medicine . . . within the next few decades, this area of science is going to transform medicine - I think there's little question about that."

But, he cautioned, "it's hard to say which treatments and which areas will be first," and at this point, public expectations appear to be somewhat inversely proportional to the likely timeline of clinical relevance. He added, "it's fair to say that transplantation of pluripotent cells is probably not on the immediate horizon."

Instead, much more immediate uses might come in drug screening. George Daley, whose laboratory is on the forefront of research into induced pluripotent, or iPS cells, said in his talk on "Patient-Specific Pluripotent Stem Cells" that his laboratory has used the technique to make a variety of cell lines modeling various disease states, which could be used to study the cell biology of those diseases.

Transplantation, though it has captured the public's imagination to a far greater degree, most likely has a much longer road. For one thing, getting cells to differentiate into a specific and functional cell types is still much more art than science.

Researchers were optimistic that, ultimately, such differentiation would be not just possible, but possible in multiple ways. Kenneth Zaret from the Fox Chase Cancer Center said that his thinking on how stem cells differentiate had undergone a change over the years. "I used to think of [cell differentiation] as an exquisite watch for which there is only one solution," he told the audience in a talk on "Principles for Guiding Stem Cells to Liver and Pancreas Fates." But these days, he said, he thinks that cell development is more like what he described as "an American-style Timex watch: As long as the arms go around and it's on time, it doesn't matter what's behind the dial."

Likewise, Daley expressed confidence that "there will be more than one way to reprogram [iPS] cells."

Indeed, Zaret said, it might in some ways be easier to make more complex tissues than specific cell types. "Different cells within an emerging tissue undergo mutually inductive . . . interactions, and more significantly, it may be easier to develop differentiated tissues than single cell populations in vitro," he said.

But for the time being, it is important to stringently separate what's currently possible from what is hoped for in the future. Marcus Grompe, of Oregon Health Science University, pointedly noted that to be useful, stem cells have to not only be functional, but also transplantable. While there have been a number of reports on differentiation of stem cells into hepatocytes or liver cells, he said that in his opinion calling cells that differentiate but do not engraft after transplantation hepatocytes is a misnomer: "If they were real hepatocytes, they would transplant like real hepatocytes."

Indeed, Grompe, who gave a talk on "Challenges to Clinical Cell-Based Liver Therapy," noted that it's not really surprising, given that even cells from donors quickly de-differentiate under culture conditions - mouse hepatocytes lose their transplantability within five days. "If we can't even maintain differentiation and transplantability of mature cells, how can we hope to make such cells from stem cell sources?" he asked his audience.

Insofar as ethical considerations were touched on at the meeting, they concerned the price of any therapies more than the cell source. Daley devoted part of his talk to the tradeoffs between autologous therapies, which would not necessitate immune suppression, but would be much more expensive than possible stem cell banks modeled on the blood bank system.

In response to a question of whether such therapies would ever be cost-effective, he told the audience that "It's a challenge, and I think social justice issues speak to the need to be able to imagine applications that could be widely available," adding that the International Society for Stem Cell Research has a task forces on clinical translation with a subgroup on social justice grappling with such issues.

But, he noted, good medicine is never cheap. "Bone marrow transplantation is very expensive. Heart transplantation is very expensive. We have many patient-specific, labor-intensive, expensive therapies, and . . . I think that we have to figure out ways that we can make these broadly available," he added.