Scientists at the University of Minnesota have taken a big step toward making replacement organs with the recipients’ cells. In experiments performed on rats and pigs, the researchers stripped donor hearts of their cells to create scaffolds on which the recipients’ cells were grown. The hope is that a similar approach might someday prove useful to human patients with end-stage heart disease. In theory, these novel hearts could prove to be better than traditional donor hearts because they are less likely to cause an immune response.
“It’s an audacious, gutsy, exciting piece of work,” says Buddy Ratner, a professor of bioengineering and chemical engineering at the University of Washington, who was not involved in the research. Still, substantial hurdles remain before the approach might be applicable to human patients.
“This is just a first proof of concept, showing that it’s not completely crazy” to try to decellularize a whole heart and repopulate it with new cells, says Doris Taylor, director of the Center for Cardiovascular Repair at the University of Minnesota. Her team’s work was published yesterday in Nature Medicine online.
In order to create decellularized scaffolds, Taylor and her team perfused rat hearts with detergents. When the cells were removed, a complex architecture of white extracellular matrix remained. The anatomy of the heart chambers seemed to be intact, as did the valves and blood vessels, says Taylor.
The researchers reseeded the scaffolds with cardiac and endothelial cells taken from rats. Then they placed these constructs in bioreactors that simulated blood pressure, electrical stimulation, and other aspects of cardiac physiology. “We wanted to treat the cells as if they were in a heart and see if they behaved accordingly,” Taylor says. After four days, the cells in the hearts began to contract. After eight days, the hearts were able to pump with about 2 percent of the force of an adult rat heart, according to the paper.
“This is the ultimate biomimetic approach to cardiac tissue engineering,” says Gordana Vunjak-Novakovic, a professor of biomedical engineering at Columbia University. A decellularized whole heart matrix provides “practically an ideal scaffold,” she says, since it preserves much of the composition, structure, and mechanical properties of the heart.
In theory, if hearts could be made this way for human patients, they might offer an alternative to traditional donor hearts. Theoretically, patients would not need to take immunosuppressant drugs since the new constructs would be built with their own cells.
Still, the method would require a cadaver heart (or possibly a pig heart) from which to make the scaffold. It still “takes a heart to make a heart, and we can’t spare any hearts at the moment,” says Ratner.
Another challenge would be securing appropriate human cells–in sufficient quantity–to repopulate the scaffold. Adult heart-muscle cells, or cardiomyoctyes, do not proliferate, says Vunjak-Novakovic. Nor can these cells be made from readily available sources such as adult cells derived from bone marrow. Resident stem cells are a potential source, but they are not plentiful. Embryonic stem cells are also a possibility, but they need to be directed to differentiate into a desired tissue and customized in order to be accepted by patients.