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13 T M C » P U L S E | J U N E 2 0 1 9 In the Lab with Doris Taylor B A B A small human-sized heart hangs suspended in a bioreactor behind a maze of locked doors in Doris Taylor's lab at the Texas Heart Institute (THI). It is void of color, drained of blood and cells. All that is left is its natural scaffold of extracellular matrix, fully intact. Taylor, who is the director of regenerative medicine research at THI, has already created more than 100 of these "ghost hearts"—and she intends to keep going, pumping each of them full of hundreds of millions of stem cells, hooking them up to artificial lungs and a blood pump, then watching them grow. Eventually, she believes, scientists will use this technique to create tailor-made organs for human heart trans- plants using a patient's own stem cells. This could mean an end to organ shortages and anti- rejection drugs, as well as a revolution in cardio- vascular surgery. But bringing one bold new idea to fruition means finding solutions for all the large and small problems that arise along the way. "Ten years ago, when we discovered the con- cept of building a ghost heart, I thought stem cell biology had advanced enough that we would be able to just take stem cells, put them in the heart, and do something cool. It's taken us 10 years to develop methods to just generate enough stem cells to transplant a meaningful number in the heart," Taylor said, adding that they have now developed the ability to grow over two billion human-induced pluripotent stem cell-derived cardiomyocytes a week. "Which is unheard of," Taylor said. Cardiomyocytes are heart muscle cells. Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to mimic embryonic stem cells, though iPSCs have not yet been differentiated, meaning they have not started the process of becoming special- ized cells. In other words, iPSCs are cells with an opportunity for a fresh start, which is necessary for growing new, healthy organs. Generating the sheer number of cells required for each heart is just one of the many hurdles Taylor and her team have faced. They have also had to design and create their own methods for sterilizing the tools and environments to keep the hearts clean and healthy as the stem cells mature. But they worked through that, too, and can now keep a heart going for 60 days—a cap she's had to implement because of the availability of resources. Each custom bioreactor set-up is expensive, so her team must stop one in order to start a new one. But, she said, they are exceptionally close to successfully building a working, human-sized heart. And in the meantime, the knowledge they've gained pursuing this goal has led them to the doorstep of many other medical challenges. Location, location, location "We've learned that if we put the same stem cells in the atrium or the ventricle, they become different cells, so the matrix seems to have cues that drive differentiation and maturation, which is really cool," said Taylor, a scientist with a Ph.D. in pharmacology. "In human hearts where heart fail- ure is present, and where different kinds of heart failure is present, the scaffold is different. So all of a sudden, we're learning at an intriguing level what we already knew kind of a priori, which is that stem cells respond to their environment to become what they find themselves surrounded by." Taylor hypothesized that one of the reasons cell therapy has yielded only modest results in repairing damaged hearts is because the stem cells are being placed in unhealthy organs. ➟ Doris Taylor, Ph.D., director of regenerative medicine research at Texas Heart Institute, stands in her lab. The regenerative medicine and cell therapy pioneer shares her latest breakthroughs and the future of mending hearts :