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In Doris Taylor’s cell- and molecular-­biology lab at the University of ­Minnesota, a small pink heart beats in a glass chamber amid a complex of tubes. With each twitch, the heart’s bottom tip traces a small curve in space, and pink nutrient solution flows out through the aorta. Remarkably, this living heart was grown in the lab.

Taylor directs the university’s ­Center for Cardiovascular Repair, where her team has created bio­artificial hearts using a novel approach in which animal hearts act as scaffolds. The researchers begin with a rat or pig heart and chemically wash away its cells. What remains is the extracellular matrix, a complex of carbohydrates and proteins that preserves the intricate structure of chambers, valves, and blood vessels. The researchers add heart cells harvested from a newborn animal and incubate the organ in a bioreactor, which provides physio­logical cues like pressure and electrical stimu­lation. Soon, the heart begins to beat weakly on its own.

The goal is to create hearts and other organs for transplant that use the extracellular matrix of a cadaver’s or pig’s organ and are populated with a recipient’s cardiac progenitor cells. Since the re-created organ would essentially be made from the patient’s own cells, it would be compatible with his or her body. In theory, patients would not need harsh immunosuppressant drugs, because the bioartificial hearts would not provoke a strong immune response. “Even though heart transplants are great, you’re basically trading one disease for another,” says ­Taylor: immunosuppressants can cause high blood pressure and kidney disease. “Our hope is to overcome that.”

The idea of growing new heart tissue to repair heart damage is not new. Numerous groups are working on cell therapies, in which new cells are injected into a specific region of a failing heart to help restore function. In fact, Taylor herself helped pioneer that approach in earlier work at Duke University. Researchers are also developing patches of cardiac tissue that could be sewn to the surface of a sick heart to help it contract more strongly. But both approaches would primarily benefit patients whose heart damage is not very severe, ­Taylor says. By contrast, Taylor’s bioartificial hearts are aimed at patients who need organ transplants to live.

Taylor chose to use real hearts as a starting material because the organ’s structure is too complex to build from scratch, at least in the near term. “Nature’s already figured out a way to make this scaffold,” she says, “so why try to build it when we don’t know everything that’s there?”

Gordana Vunjak-Novakovic, a ­professor of biomedical engineering at Columbia University, says that to her knowledge, this is the first time someone has “taken a whole heart and developed a system for stripping it fully of cells” in order to create a new, recellu­larized organ. “It’s very significant work,” she adds, though it “still has a long way to go” before it could be useful to patients.

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Credit: Jonathan Chapman

Tagged: Biomedicine, molecular biology

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