From left to right: A normal pig heart, a pig heart after being decellularised, the pig heart prepared for recellularisation. Photos courtesy of the University of Minnesota.
In a medical first, University researchers have created a beating heart in the laboratory. Using detergents, they stripped away the cells from rat hearts until only the nonliving matrix, or “skeleton,” was left; they then repopulated the matrix with fresh heart cells.
If perfected, the technique may be used someday to generate new hearts for patients. In the United States alone, about 5 million people live with heart failure, 550,000 new cases are diagnosed every year, and 50,000 die waiting for a donor heart.
“The results were a home run,” says Doris Taylor, director of the University’s Center for Cardiovascular Repair and a principal investigator on the study. “We knew that cell therapy–that is, transplanting cells into [a patient's damaged] heart–is not a panacea. So we started thinking, ‘Is there a way to use cells to engineer heart tissue?’”
The idea, she says, is to create whole new blood vessels or organs by implanting a patient’s own cells into a matrix derived from a donor organ. This approach ought to bypass the problem of organ rejection because the matrix, being devoid of cells, shouldn’t provoke an immune response. Even if it did, the new cells would create a fresh matrix of their own, which would turn off the immune response and free patients from the need to take immunosuppressive drugs.
The process, called whole organ recellularization, can be done “with virtually any organ,” Taylor says.
A simple plan
The main hurdle in creating new hearts wasn’t finding the right cells but recreating the vastly complex architecture of the heart, Taylor explains. In puzzling it over, she and Harald Ott, a research associate in the center (now a surgical resident at Harvard Medical School and first author of the study), hit on a way to get nature to solve the problem for them.
To remove cells from fresh rat hearts, the researchers pumped solutions of detergents through the network of blood vessels that normally nourish the organ. The treatment popped all the cells like balloons and washed away the debris, leaving the matrix of protein fibers that form the backbone of a living heart’s connective tissue. It’s called the extracellular matrix, or ECM.
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