Speakers Chart Directions in Stem Cell Research

Photo by Steve Gilbert In mice, Amy Wagers is tracking down and characterizing the stem cell–like precursor cells that provide skeletal muscle with its long-known regenerative powers.

Embryonic stem cell research may be divisive in some places, but at Harvard the potential of stem cells for understanding and treating disease has been a unifying force, researchers told the alumni who crowded into the HMS Faculty Symposium on June 8.

More than 100 faculty members have rallied around the full spectrum of questions from biology to ethics. Lab meetings of the Harvard Stem Cell Institute can swell to as many as 250 scientists. Philanthropic efforts at HMS and affiliated institutions have merged crucial private financial support.

“The cooperation across the University is an important change in the way we do business,” said George Thibault, the Daniel D. Federman, MD professor of medicine and medical education at HMS and Brigham and Women’s Hospital, who introduced the session.

“We think it is the most concentrated effort in the world,” said moderator David Scadden, co-director of the institute, HMS professor of medicine at Massachusetts General Hospital, and director of the MGH Center for Regenerative Medicine.

The science itself seems to be following suit as preliminary results begin to show common themes across a range of approaches, animal models, and human tissues. Jeffrey Macklis, HMS associate professor of surgery at MGH, and his colleagues, for example, have been able to rebuild elements of the nervous system in fully adult mouse brains by identifying the molecular controls over neural precursors (“stem cells”) and discovering and directing the normal signals that allow stem cells to repair and regenerate tissue. Likewise, Amy Wagers, an HMS assistant professor of pathology at Joslin Diabetes Center, is starting to define lineages from the earliest muscle progenitor cells she can find in adult mice.

Talk of future medical applications of stem cells most often evokes visions of providing replacement parts for malfunctioning or diseased tissue, but scientists are investigating at least three other big ideas, Scadden said. Some researchers want to understand the endogenous repair systems and how drugs may modify the activity of resident stem cells. Other groups are looking for cancer stem cells that may be the elusive source of tumor tissue and a new specific target for anticancer drugs. Finally, others are using embryonic stem cells to create animal models of disease and to test new therapeutic approaches.

It will be at least 10 years before the first application of embryonic stem cell research reaches a patient, and the application will likely involve blood cells, predicted Leonard Zon, a Howard Hughes investigator and the Grousbeck professor of pediatrics at HMS and Children’s Hospital Boston, who models human disease in zebrafish.

Part of the extended timeline includes extensive administrative and regulatory review to ensure thorough ethical consideration, Zon said. For example, it took two years and several oversight bodies within the institutions for the Children’s Hospital laboratory of George Daley to win permission to create human embryonic stem cell lines using nuclear transfer with human eggs and embryos. It is believed to be the first noncommercial effort in this country to use human embryonic stem cells to try to replicate successful animal experiments. This major step was announced June 6.

The same technology can be used for reproductive cloning, Scadden explained in response to a question from the audience, but stem cell researchers adamantly oppose such applications. Unfortunately, despite the federal restrictions on human embryonic stem cell lines, there is no national discussion or regulation to block unethical stem cell applications. And only a few states, such as Massachusetts and California, have enacted such restrictions. “It’s an important discussion to get engaged in,” Scadden said.

—Carol Cruzan Morton

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