Doris Taylor’s favorite video is “The Matrix.” Not the film starring Keanu Reeves, but a short movie of a beating heart that was e-mailed to her at 3 a.m. It was the spring of 2005, and the sender was Harald Ott, then a postdoctoral fellow at the University of Minnesota who was working with Taylor.
“The sad but true fact was that it was three in the morning, but I was in my office,” Taylor recalls. “Harald sent me the video and then called me. I watched the video, called him right back, and said, ‘You’ve got to be kidding.’ It was a eureka, fist-in-the-air, ‘Yes!’ moment.”
Why the elation? Because that beating rat heart could revolutionize organ transplants and save millions of lives.
Through a process called whole-organ decellularization, Taylor’s research team had slowly drained all the cells from the heart, leaving only the extracellular matrix—the framework between the cells—intact. “You can think of it as a scaffold, a bare wooden frame for a house,” Taylor says. “Decellularization had previously been applied to simple structures, like heart valves, or thin structures, like a blood vessel, but not successfully to whole organs. We developed a proprietary method to infuse decellularization agents into the blood vessels of an organ and wash the cells out from the inside out.”
Next, they repopulated the heart with a mixture of cell types—stem cells, progenitor cells, muscle cells, and others—from the minced hearts of newborn rats. And then the matrix, fed with nutrients and oxygen that would normally be carried by blood, was watched around the clock. Four days later, the cells began to contract; four days after that, the heart was able to pump fluid out of its aorta.
“Scientists have grown heart cells in a dish, but over a few days they usually die or stop functioning,” Taylor says. “Heart cells need a lot of oxygen, so if you build something more than a few cells thick, the cells in the middle die because they can’t get oxygen. Making a complex thick heart wall had been impossible due to a lack of blood vessels or other artificial ways to get blood and oxygen in there. Our process retains the holes where the blood vessels used to be so we can feed the cells we put back in.”
Creating a whole organ and using nature’s own matrix for building and feeding the new heart were both breakthrough aspects of the project. Another was simply finding that the mix of new cells would synthesize and work in concert.
“The cells we put in were immature heart cells that were not connected to each other,” Taylor explains. “So having something that coalesced and formed a synchronously beating organ was pretty remarkable. There were so many places we could have failed,” she adds, but “everything worked, and the result was essentially a new beating heart from a cadaver organ.”
The implications are staggering. Nearly 5 million people live with heart failure in the United States. Up to 50,000 of them die annually waiting for a donor heart. Since a bioartificial heart could be built in weeks, the dire shortage of donor organs could be relieved through Taylor’s work. Such hearts might eventually be made from pig-heart scaffolds repopulated with a patient’s own stem cells or less malleable progenitor cells, or they might be built from human hearts that are ineligible for transplantation because they were harvested more than four hours after the donor’s death.
Either way, the potential is now there to use a scaffold that otherwise would not have been usable. And if a person’s own cells are used to create the transplant organ, that might eliminate the need for harsh anti-rejection drugs, which can damage the recipient so badly that another transplant is required.
Taylor’s team has experimented on a heart, but the technology could be applied to virtually any organ, she says. And as her team continues to advance its research, the possible applications multiply.
“Building a whole organ is pretty complicated, and yet building pieces of organs may not be as complex,” she says. “Growing a piece of heart for a kid with a congenital heart abnormality might be good enough.”
As for other therapies, “one of the products on the market right now is an artificial skin. If we decellularize skin—and we can—could we use that to treat burns? Could you grow your own cells back into that?” Taylor asks. “Our hope is that because we can do this with any organ or any tissue that gets a blood supply, we can think about building a pancreas for kids with diabetes,” a lung for someone with cystic fibrosis, new blood vessels for bypass grafting—“the potential here is huge.”
Her technology could also be put to use by the pharmaceutical industry. “A number of drugs never make it past clinical studies because of toxicity, usually due to liver or heart problems,” Taylor continues. If a heart or liver or kidney could be grown on a scaffold in the laboratory, “then we could in theory test drugs on those and eliminate the drugs that are most toxic before they ever reach a person. We’re pretty excited about that.”
Ever since Taylor and Ott’s breakthrough was published in the online edition of Nature Medicine in January 2008, the medical research community has been buzzing about “the beating heart in a jar.” “There are a lot of people who are now doing similar things based on what we’ve done,” Taylor says. “I get a lot of e-mails asking me how to do it.”
She also hears from people desperate for transplant organs to help their loved ones. “When you get a letter from a parent, and you’re not there yet, it’s hard,” Taylor says. “So a lot of our experiments have names on them now. I don’t mean that literally, but what I mean is we understand the people who need these, and we’re working very hard to try to move forward in a smart way, but as quickly as possible.”