Grant funds effort to generate heart tissue with stem cells

Singers have long crooned about ways to mend a broken heart, but engineering and medical researchers at Stanford are discovering how to make new tissue to do the job. Funded by a new type of $2 million, four-year grant from the National Science Foundation (NSF), the multidisciplinary team hopes to learn how electrical, mechanical and chemical stimulation can be applied to stem cells to generate tissue for repairing damage, such as that caused by heart attacks.

"We want to guide researchers in what kinds of stimuli are important," says mechanical engineering Assistant Professor Beth Pruitt, who leads the NSF project. "We are developing bioreactors that allow us to vary those conditions and to produce coordinated beating tissues that are aligned and appear functional. If we are lucky, the last phase is in vivo model testing. Hopefully we'll see that they improve cardiovascular function."

The collaboration among Pruitt, materials science and engineering Assistant Professor Sarah Heilshorn, mechanical engineering Assistant Professor Ellen Kuhl, radiology and medicine Assistant Professor Joseph Wu and surgery Professor Christopher Zarins is funded by a new NSF award program called Emerging Frontiers in Research and Innovation. The program promotes multidisciplinary research by bringing together teams of NSF managers in an annual competition to identify promising themes at the intersection of different scientific disciplines. The NSF then looks for similarly multidisciplinary groups of researchers with promising ideas along those lines. The theme of Stanford's grant is "Cellular and Biomolecular Engineering."

Stem cells, like wild cards in a poker hand, can become a myriad of other cells with specific physiological functions, such as heart muscle. Previous researchers have chemically stimulated individual stem cells to transform, or "differentiate," into heart muscle cells, Pruitt says, but what remains undiscovered is how to optimize the stimulation to create aligned, coordinated whole tissues that make a real medical difference when they are implanted in a heart. In the case of heart tissue, the desired cohesion includes synchronized beating motion.

To determine the conditions that allow for the creation of such coordinated tissues, the team will engineer testbeds in which they will be able to expose stem cells to different combinations of electric fields, mechanical forces and biochemical solutions in search of optimal combinations.

One testbed will be a flat, stretchy sheet of a silicone-like material that is machined at the nanoscale with electrodes and microfluidics to allow for controlled experiments on arrays of cells placed inside. Another environment will be a three-dimensional mass of artificial tissue scaffolding, akin to a cube of Jell-O, in which cells will be suspended and exposed to different stimuli.

Each of the Stanford researchers on the team brings essential expertise to the project. Pruitt studies and measures mechanical forces at the cellular scale; Heilshorn develops materials for tissue engineering; Kuhl creates computational models of tissue remodeling; Wu has developed tools for imaging and tracking stem cells as they differentiate; and Zarins specializes in heart disease and vascular biology.

Pruitt, Wu and Zarins began working together last year on aspects of the work with funding from the National Institutes of Health and the California Institute for Regenerative Medicine.

David Orenstein is the communications and public relations manager for the Stanford School of Engineering.

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