Cardiovascular: Reaching for a Cure: UCSF, February 2011

The heart cannot adequately regenerate damaged tissue after a heart attack. But could stem cells help it along that path? Doctors and researchers at UCSF with a wide range of expertise are exploring this possibility together, working to see whether stem cell therapies might pump some regenerative power into the heart.

Working within a so-called pipeline designed to move basic research discoveries into studies in animals and, eventually, in humans, the scientists and clinicians work with all sorts of patients, and on all rungs of the research ladder, in the hope of reaching a cure faster.

The effort starts in early-stage labs like those of developmental biologist Deepak Srivastava, MD, and cell biologist Harold Bernstein, MD, PhD. It extends to clinicians like Yerem Yeghiazarians, MD, who can look at how the cells interact once they’re in the body.

Srivastava, director of the Gladstone Institute of Cardiovascular Disease, brings expertise as a pediatric cardiologist to his leadership of the cardiology pipeline. The other leader, Yeghiazarians, as co-director of the Adult Cardiac Catheterization Laboratory, works with adults.

“We are always looking for areas of synergy where expertise from one group can be leveraged by the other groups,” Srivastava says.

Srivastava’s lab looks at the way a stem cell can differentiate and become a cardiac muscle cell. Bernstein’s lab focuses on later stages of the differentiation process, often applying what he’s learned from Srivastava’s findings to his own study of how different types of heart muscle cells develop.

For instance, both Srivastava and Bernstein are interested in how molecular tools known as microRNAs regulate the development of heart muscle cells. They collaborated on a study in which Bernstein’s lab formed cardiac cells from human embryonic stem cells, and Srivastava’s lab examined how microRNAs formed in those cells.

“The work of Dr. Bernstein – finding new ways to identify these cardiac cells that are derived from stem cells – has been helpful to us,” Srivastava says.

Bernstein returns the compliment. “We were able to do pretty significant work together,” he says.

Once Bernstein and Srivastava figure things out on a cellular level, Yeghiazarians “figures out the best way to get them into damaged tissue,” Bernstein says. “We can ask a lot of questions in a dish about what’s going on at the molecular level, but in the real world, the cells are behaving in the context of an organ. He provides an important part of this kind of analysis.”

Yeghiazarians, who also directs the UCSF Translational Cardiac Stem Cell Program, has the clinical expertise to tackle problems such as how to get the cells into the heart and how to get them to stay there once they’re implanted – and ultimately do the job they’re assigned.

“It’s a beautiful pipeline that’s been set up because you can go from A to Z entirely within UCSF,” he says, “We have the ability and the expertise to do all of these types of studies together.”


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