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The Regenerative Promise of Stem Cells

At Alpert Foundation Prize Symposium, researchers define new challenges

Howard Green, winner of the 2010 Warren Alpert Foundation Prize, was honored at a symposium on Sept. 27. At the event (from left) are Dean Jeffrey S. Flier; Elaine Fuchs; Green; Bevin Kaplan, senior director of the Warren Alpert Foundation; Konrad Hochedlinger; and George Daley. Photo by Suzanne Camarata.

New research is illuminating the benefits—and the challenges—of working with stem cells, scientists said at the 2010 Warren Alpert Foundation Prize Symposium.

“Scientific findings in this tremendous field are appearing at an astonishing rate,” Dean Jeffrey Flier told an audience of more than 500 scientists at the Sept. 27 symposium, Exploring Stem Cell Biology and Regenerative Medicine. “And they reveal the complexity of the field as well as the extraordinary capacity that it has to change biology and human health.”

The presenters, including David Scadden, Elaine Fuchs, George Daley and Konrad Hochedlinger, discussed their work in a tribute to Howard Green, the George Higginson Professor of Cell Biology and recipient of the 2010 Warren Alpert Foundation Prize. Green cultivated adult stem cells in the lab to generate skin grafts for burn patients around the world, and, in the process, he built a foundation for future work with stem cells.

“All fields stand on the shoulders of giants, and I have to say none in the field of stem cell biology and stem cell medicine has been taller than Dr. Green,” said Scadden, the Gerald and Darlene Jordan Professor of Medicine at HMS and Massachusetts General Hospital.

The Alpert Foundation Prize, initiated in 1986 by philanthropist Warren Alpert, honors researchers for medical discoveries with an impact, whether realized or potential, on human health. The recipient receives an award of $200,000.

Applications in Sight

Scadden highlighted three broad applications for stem cells. Stem cells should prove useful, he said, in high-throughput screening methods for drug discovery; as models to understand the molecular basis of disease; and, ultimately, as a cell population that in some ways represents a personalized toolkit for humans. Scadden, like his fellow speakers, bridges these categories in his own research, which focuses on blood formation and diseases, including AIDS and cancer.

In George Daley’s laboratory at Children’s Hospital, the HMS professor of biological chemistry and molecular pharmacology works with induced pluripotent stem (iPS) cells, modeling diseases that range from amyotrophic lateral sclerosis (ALS) to immunodeficiency disorders. “We have now put together an iPS core,” Daley said, referring to the Harvard Stem Cell Institute’s shared core facility at Massachusetts General Hospital, where iPS cells are derived, stored and made available to the scientific community. “There is an enormous appetite for using these disease-specific stem cell lines for various aspects of research.”

But iPS cells also pose challenges. In July 2010, Daley’s team published a paper online concluding that, unlike embryonic stem (ES) cells, iPS cells, which are reprogrammed adult cells, retain a memory of their former role. At the same time, Hochedlinger’s lab reported similar findings.

“Many researchers have observed that iPS cells fair more poorly in differentiation and development,” said Hochedlinger, HMS assistant professor of medicine at MGH. The recent studies examined methylation patterns, signals that help each cell pass along its specific identity—epithelium or pancreas, for example—by specifying which genes are expressed. “Over the last few years, several reports have been published suggesting that hundreds of microRNAs’ methylation patterns are distinct between iPS and ES cells in both mouse and human,” Hochedlinger said.

Given the differences between iPS cells and embryonic stem cells, “It is still too early to eliminate embryonic stem cells from our toolkit,” Daley said.

And it is also too early given the therapeutic potential of the field. Stem cells may one day prove useful in treating a range of diseases and injuries from Alzheimer’s to Parkinson’s to stroke, Flier said. “Being a diabetes researcher myself,” he said, “I truly think that we might at one point have the capacity to replace insulin-producing beta cells in people with type 1 diabetes.”

Hurdles Ahead

One challenge to stem cell research lies beyond the power of bench science to surmount: the politics of stem cells derived from human embryos. “Research on these stem cell lines, as everyone knows, is controversial for a whole variety of reasons,” Flier said, “and the on-again, off-again nature of federal funding to support the work remains of deep concern to many members of our community and people around this country and beyond.”

In his remarks, Green warned that creeping regulation threatened the very kinds of discoveries the Alpert Prize was celebrating. Today’s rules, he said, could well have prevented the collaboration that led to his pioneering work with burn patients. “At the time this work was carried out, there were no regulatory problems, no hospital committees—the FDA was not interested,” he said. “This procedure, if I had not done it at that time, I think that it would not have been discovered by others.”

Green also stressed the importance of basic research unbound by narrow objectives. “What is basic research?” Green asked. In quoting rocket scientist Werner von Braun, he stressed the importance of pursuing knowledge wherever it may lead: “Basic research is what I am doing when I don’t know what I am doing.”

Green’s legacy extends to the many researchers—now leaders in the field—who cut their teeth in his laboratory. Elaine Fuchs, president of the International Society of Stem Cell Research, took the podium after Green. Once a postdoctoral fellow in Green’s laboratory at HMS and now a professor of cell biology at Rockefeller University, Fuchs discussed her research into the molecular mechanisms by which skin stem cells regenerate and differentiate.

Her lab has explored the role of stem cells in skin cancer, but is perhaps better known for inducing hair growth in mice. “Throughout your lifetime, if you’re lucky—and Howard, I’m sorry about this—your hairs will not only undergo periods of rest, but also undergo periods of growth,” she told her former mentor, to the amusement of those assembled.

A video of the talks at the Warren Alpert Foundation Prize Symposium will soon appear online at http://www.warrenalpert.org