The lub-dub of a healthy heart  pg. 7

Part of the “putting them together” means getting the matrix right.

If you look at a heart valve, it’s mostly not cells; it’s mostly matrix,” Barnett says.

“We know a lot about the cells – we know one when we see one, and we know a lot about the factors that make those cells transform,” he continues. “But as far as what’s in that matrix, I could fall in a bucket of it tomorrow and not really know what I was in. It’s the missing component right now.”

Richard Caprioli, Ph.D., who directs the Vanderbilt Mass Spectrometry Research Center, will lead efforts by the SysCODE consortium to de-mystify the matrix by identifying the proteins in the cardiac jelly that are important in valve development.

Already, tissue engineers in Boston are making “gel substrates” of hyaluronic acid – the matrix component Baldwin identified as important for heart development. “As we learn what other components are in the matrix, and how they’re organized, our Boston colleagues can make and incorporate those things into the gel,” Barnett says, to create the best “scaffolding” for a heart valve.

Ultimately, to grow a valve in the lab may take more than the right scaffolding and the right cells, Barnett and Baldwin acknowledge. The remodeling that takes place after the cells are in the cushion matrix in vivo may require pulsatile blood flow, and the investigators are in conversation with the tissue engineers about how to potentially replicate that flow in vitro.

The parts will come together, these investigators say.

“It sounds like science fiction, but it will happen in my lifetime, there’s no question,” Baldwin says. “There’s no inherent design limitation; the only thing we don’t have is all the information, which is what we need to get.”

The investigators are also optimistic that SysCODE’s unraveling of the developmental biology “programs” for heart valves, teeth and pancreas will turn up common signaling pathways and explain why it looks like valves turn into bone – become stiff and calcified – when they’re diseased.

“We think that maybe when the valve is injured, it reactivates developmental programs to try to repair itself; only now these are not appropriate,” Baldwin says. “If we understand the developmental program, I think we’re also going to figure out what the pathological program is … and if you can find something to prevent aortic valve calcification as people age, that’s going to have a huge world health impact.”

The radio folks leaving the conference room seem convinced. “That was cool,” says one. “It’s incredible what these researchers can do.”

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