TMC PULSE

14 T M C » P U L S E | J U N E 2 0 1 9 "We're taking these immature cells, stem or progenitor cells, and we're putting them in a scar. And we're saying, 'Hey, grow up and become a healthy heart,'" Taylor said. "But what if we put them in a matrix before we put them in the heart and allow them to mature first?" Her lab has been working on a cardiac patch that may be more successful than traditional cell therapy techniques. Currently, they are pursuing two different methods: the first involves taking a piece of decellularized healthy heart, cutting it out, then sewing it onto the surface of the heart as a patch; the second involves grinding up one of the ghost hearts and creating a powder that they then convert into a gel that is injected into the scarred or damaged area of the heart. "It's really about putting things in the right environment and letting them do their thing," Taylor said. "I call it the real estate approach to cell therapy. Location, location, location." A step further There's more—in fact, potential applications for the team's discoveries are vast. After noticing that individuals with heart fail- ure seemed to have different matrices than those with healthy hearts, Taylor wanted to compare the matrices in the hearts of animals. What her team found was that in young animals, the matrices of the heart, liver and kidneys of females were stiffer than those of their male counterparts. Taylor was puzzled. Why would that be? "I started thinking about the fact that when women get pregnant, their blood volume goes way up," she said. "And if your heart has to pump against that blood volume, you need something that's tougher. We also found out that if we look in older males and females, the males catch up with the females later in life." Taylor took it a step further, aware that a disproportionate number of women suffer from a type of heart failure called preserved ejection fraction systolic dysfunction, in which the heart muscle contracts normally, but the ventricles do not relax as they should. "It's the ultimate irony," she joked. "Women can't relax as well." It turns out, there is a protein in the heart mus- cle responsible for that stiffness. "We've recently found that the extracellular matrix determines how much of that protein you have," Taylor said. "This type of heart failure is three times more prevalent in women, and I think it's because the matrix is different, so we've developed a treatment that we hope to try over the next year in preclinical studies that we think will reverse that." Currently, Taylor said, there are no treatment options for this type of heart failure. "It's all because we looked at the matrix and saw that there is this underlying structural dif- ference that tells cells how to behave. Again, it's about environment—location," she said. Taylor's lab is also learning that lifestyle can impact the health of a person's stem cells. "We've found that smoking, diabetes, hyper- tension—all of those things change your bone marrow, they change the cells that are there. They will increase inflammatory cells and decrease pos- itive cells, and we've been able to show … that if you look at the onset of heart disease and the loss of some of these stem cells, they absolutely mirror each other," Taylor said. "And so I say that aging, and a lot of the diseases associated with aging, are a failure of endogenous repair, and a failure of your stem cells." Taylor applied these lessons to her own life. "I was involved in a clinical study that shows when you exercise you increase the number of stem cells in your blood," she said. "And I did a study with a colleague in California where we studied acupuncture. It was a small number of women, but in the women who got acupuncture versus sham acupuncture, the number of circulat- ing progenitor cells went up—so all these things we've been told to do to decrease stress, it actually does increase the number of circulating cells." ➟

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