Phoenix Heart: Replacing a heart’s cells could ease transplants

In a step toward growing complex organs for transplants, researchers have stripped all the cells from dead rat hearts and injected the gelatinous empty structures with living heart cells from newborn rats. Eight days later, the repopulated hearts were beating, albeit feebly.

EMPTY HEART. Running a detergent through a rat’s heart (left) gradually purges the heart of its cells (center), leaving behind a translucent protein scaffolding (right). T. Matthiesen, Univ. of Minnesota

Eventually, doctors might be able to use this approach to make new hearts or other organs for transplantation by growing a patient’s own cells inside a hollowed-out organ from a pig or cadaver. Because the cells are derived from the patient, his or her body would be less likely to reject the organ.

Such reconstructed organs, however, are still years away, the researchers caution.

Animal tissues denuded of cells are already commercially available for transplant into people, but these tissues are only pieces of organs, such as heart valves. The new research marks the first time that scientists have swapped out cells in an entire heart.

A team led by Doris A. Taylor of the University of Minnesota in Minneapolis took hearts from rats that had been dead for less than 18 hours, and flushed them with a liquid detergent. The detergent gradually broke up the dead cells and rinsed them away, leaving behind translucent, heart-shaped masses of collagen and other proteins that normally surround heart cells and hold them together.

The resulting cellfree heart served as a three-dimensional scaffolding in which the new cells could grow. Providing a good 3-D framework has been one of the major challenges for scientists trying to grow replacement tissues and organs.

“The beauty of this approach is that [the team] developed a method to obtain the ultimate biological scaffold,” comments Gordana Vunjak-Novakovic, a biomedical engineer at Columbia University in New York City.

However, Taylor’s team didn’t know whether the heart cells they took from newborn rats and injected into the hollowed-out hearts would take hold and behave normally. “The fact that we can get these cells to beat synchronously is incredibly encouraging,” Taylor says.

The injected cells did not fully populate the heart lattices, and the arrangement of cells was much simpler than in the original hearts. The reconstructed hearts could pump blood at about 2 percent of the rate of a normal adult-rat heart, the researchers report in the February Nature Medicine.

Taylor is “showing proof of concept, which is very important,” comments Stephen F. Badylak of the University of Pittsburgh, who has also done research on removing cells from organs.

“The tricky part is going to be the [new] cell population,” Badylak adds. Unlike in rats, taking cells from newborns would obviously not be a feasible way to reseed hearts for humans, and in any case newborns’ cells don’t have the mobility or flexibility to fully repopulate a heart. More research is needed to show whether stem cells from a patient’s blood or heart tissue could do the job, Taylor says.

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