Stem cell therapy breakthrough

Researchers in San Francisco have discovered a new way to nudge human embryonic stem cells to form specialized cells - a potentially huge step toward the development of stem cell therapies to repair damaged hearts, nerves and other organs.

In a scientific first, a research team at the Gladstone Institute of Cardiovascular Disease and UCSF demonstrated that small regulatory molecules called microRNAs can influence embryonic stem cells to produce heart muscle cells.

The study, published Wednesday in the journal Cell Stem Cell, suggests that the hundreds of different microRNAs naturally occurring in the body could provide key tools to control the differentiation of stem cells into the more specific cell types needed to treat ailments such as heart defects and spinal cord injuries.

Stem cell companies are likely to scrutinize the findings for possible applications to their work, said Ralph Snodgrass, chief executive of VistaGen Therapeutics Inc., a South San Francisco company that uses specialized stem cells to test experimental drugs for heart or liver toxicity and other factors.

"We certainly welcome the ability to find other ways to manipulate, control and guide the differentiation of embryonic stem cells toward therapeutic and commercially important mature cells," Snodgrass said. Embryonic stem cells, which are usually derived from early-stage embryos, retain the ability to morph into any body-cell type.

The role of microRNAs was virtually unknown six or seven years ago, said Deepak Srivastava, director of the Gladstone Institute and co-author of the study. Now they're one of the hottest leads to understanding how the body's cells, each containing the same DNA, can develop into a wide variety of specialized cells such as bone, red blood cells and beating heart muscle. The small microRNA molecules, whose structure is related to DNA, are believed to help control which genes are active in a cell and which are silenced.

Scientists had noted that the presence of microRNAs seemed to be essential to the embryo's formation of heart muscle, Srivastava said. But he said his Mission Bay lab team and their UCSF colleagues were the first to show exactly how individual microRNAs guide embryonic stem cells to follow a path toward transformation to one type of cell while abandoning other choices.

The two microRNAs studied by the Gladstone-UCSF team not only promoted the development of cell types that give rise to heart muscle, but also suppressed genes that help create other kinds of tissue, such as nerve fibers.

That power to suppress unwanted cell types could be crucial to the use of stem cells as therapies to repair damaged organs, Srivastava said.

"You don't want bone or teeth or hair growing in the heart," he said.

Snodgrass said he could see at least three ways to use microRNAs if they do turn out to play an important role in producing varied cell types from embryonic stem cells. First, the regulatory molecules might help produce replacement tissues grown in the lab. Second, the microRNAs themselves might be used as treatments, delivered into damaged tissue, to signal the body's stem cells to make replacement cells for repair. Third, microRNAs could provide tools to create specialized cells from stem cells for drug testing.

VistaGen already has a repertoire of growth factors and signaling molecules to turn stem cells into varied cell types, Snodgrass said. But those molecules tend to be much larger than microRNAs, whose small size might make them better drug candidates, he said, because they would be easier to deliver into the body.

The majority of the financial support for the Gladstone-UCSF study came from the California Institute for Regenerative Medicine, a $3 billion taxpayer-supported stem cell research funding program created through the passage of a state voter initiative in 2004.

E-mail Bernadette Tansey at [email protected].