by Maggie Galehouse, Houston Chronicle, January 23, 2013
Doris Taylor and her team are building new organs, hoping to reverse disease, maybe even the aging process
It sounds like science fiction, but it is isn't.
On the ninth floor of the Texas Heart Institute's Denton Cooley building, Doris Taylor and her team are building human hearts, with help from pigs and stem cells.
"We think a pig heart is a perfect scaffold for a human heart, based on its structure and size," says Taylor, a passionate scientist with a Ph.D. in pharmacology.
One recent morning, a pig heart hung suspended in a clear homemade tank in the lab built for Taylor and her team. Filled with detergent, the heart had expanded to the size of a large man's fist, excess liquid dripping slowly out its sides.
Once the heart is thoroughly cleaned, hard-working human stem cells - immature cells found in our organs and tissues that help repair damage on a daily basis - will bring it to life.
"We can take stems cells from bone marrow, blood or fat and place them onto a heart, liver or lung scaffold," Taylor explains. "My motto for a long time has been 'Give nature the tools and get out of the way.' "
A pioneer in regenerative medicine research and cell therapy, Taylor arrived at the institute - at St. Luke's Episcopal Hospital - last April. She came from the University of Minnesota, where she won international attention for her work with "whole-organ decellularization" - removing the existing cells from the hearts of lab animals and humans to leave a framework to build new organs.
Cleaning pig hearts of their cells takes about two days, using the same detergent found in baby shampoo. Arranged around a sink in the lab where the team washes up, clean animal organs in different size jars await attention: livers, kidneys, an aorta, heart valves. Surgical instruments are laid out on small green cloths along the counters.
"Here are little rat hearts getting their cells washed out," says Taylor, pointing to nickel-size hearts in specially designed sterile glass containers she likens to "Rube Goldberg contraptions."
A significant unmet need
Heart failure affects nearly 5 million Americans and is the only major cardiovascular disorder on the rise. An estimated 400,000 to 700,000 new cases of heart failure are diagnosed each year, according to the Heart Failure Society of America, and deaths in the U.S. from this condition have more than doubled since 1979, averaging 250,000 annually.
On any given day, about 3,000 people in the U.S. are on the waiting list for a heart transplant, with wait times varying from days to several months, according to the National Heart, Lung, and Blood Institute. Only 2,000 donor hearts are available each year.
"Unlike some other organs, hearts have a very short window for transplants - four hours," Taylor explains. "Just think about Texas. If someone in Tyler needs a heart and the heart is in Amarillo, you're pushing the window even in our own state."
Mechanical devices are certainly becoming more of an option, she continues, but there are complications; the devices aren't perfect.
In addition, the population is aging, and we're keeping people alive longer after heart attacks, she adds. And you can't take an organ from a living person.
"You put all those things together and there's a significant unmet need for the work we're doing," Taylor says.
Beyond building healthy new hearts, Taylor's research could help medicine in myriad ways. Hearts and other animal organs reanimated with human stem cells could be used in transplants and emergency situations, she says. More broadly, the technology could make mechanical hearts work better, grow skin for burn centers and build a dialysis device for acute liver failure.
Her stem cell research could be used to reverse the aging process.
The work is as much about prevention as creation.
As we age, we have fewer stem cells, Taylor explains, and the ones we have don't work as well:
"If you know that everyone in your family dies of a heart attack around 65, then I want some stem cells from you now so we can save them and grow them and intervene early to reverse the disease."
Reverse disease? Reverse the aging process?
"I've been called Dr. Frankenstein more times than I care to admit," Taylor says, with a wry smile.
A beautiful design
Living hearts get their color from blood and myoglobin. Washed clean of their cells, the ivory-hued pig hearts and other organs around Taylor's lab seem other-worldly. They look like mysterious sea creatures, delicately constructed yet strong and fibrous to the touch.
One of Taylor's colleagues, Brazilian cardiac surgeon Luis Sampaio, picks up a pig heart and pulls it apart gently to reveal the main valve.
"The beauty of the valve is that it closes up when it's supposed to," Sampaio says. "It's a beautiful design. A one-way street of pumping."
Taylor and her team will add stem cells to the heart one of two ways: by inserting a tube in the aorta and letting the cells drip inside, or by injecting the cells with a syringe through the wall of the heart.
A heartbeat is perceptible after just a few days. Within a few weeks, the heart is strong enough to pump blood.
"It's almost like time-lapse photography," Taylor says.
The stem cells used come from patients who've given Taylor permission to examine their cells and, occasionally, from companies that sell cells. The ultimate goal is to use a person's own stem cells to fight disease, but cells from other people can also be viable.
"I would use your cells and cells that wouldn't be rejected by you," Taylor explains.
As a scientist, she understands that the nature of her work makes some people uncomfortable.
But for her, it boils down to this:
"It would be impossible for me to look a parent in the face and say I didn't use every tool I know about to make your child better."
Two more years
Now in her early 50s, Taylor grew up mostly in Mississippi, where she moved with her mother and siblings after her father died of cancer.
"I remember thinking I didn't want anyone in the world to have to go through that," she said, recalling her dad's death. She was 6.
Taylor's mother, a librarian, told her and her siblings they could do anything they wanted.
"I've always been curious," Taylor says. "I always wanted to know how things worked. When I was a kid, around 8, 9 and 10, I got up on Saturday mornings and tried to invent things. I thought that's what grown-ups did."
Taylor says she couldn't do what she does without the support of her team of scientists, surgeons, engineers and support staff.
"I'm lucky Jim Willerson, the president of Texas Heart Institute, believed in me enough to bring me here and let me work with this fantastic team of individuals," she says.
Taylor predicts that in the next two years, she and her team will approach the U.S. Food and Drug Administration and ask to do a first-in-human study with the bio-artificial hearts.
"Will it be a whole heart? Probably not," Taylor says. "But it could be a cardiac patch or a valve. We might start with a piece to show the safety and efficacy of the technology."
Regenerating hearts means stepping out there and taking risks. It means thinking big and not being afraid to fail. Taylor is comfortable with that.
A quote from Gandhi that she keeps on her desk says: "First they ignore you, then they laugh at you, then they fight you, then you win."