Researcher Probes Science to Building a “Bio-Artificial” Heart

Xconomy Texas — 

Most of our organs contain enough stem cells to repair and regenerate themselves after injuries. But not the heart, that most central of muscles. And finding a way to compensate for that fact has become a life’s mission for Doris Taylor, a new arrival at the Texas Heart Institute in Houston.

Taylor is a pioneer in regenerative medicine, having arrived last year from the University of Minnesota, where she gained international renown for her work in whole-organ decellularization. That’s the process of removing living cells from the organs of lab animals in order to strip them down to a matrix of tissue that can act as the scaffolding for new organs.

“At Texas Heart, we can really combine medicine and science to push new boundaries,” she says. “There’s an excitement here and level of opportunity and enthusiasm that you don’t see many places these days.”

She hopes to approach the U.S. Food and Drug Administration next year to do a first-in-human study with bio-artificial hearts.

Taylor will use her expertise as the new director of the Center for Cell and Organ Biotechnology, a recently announced $3 million collaboration between the Texas Heart Institute and Texas A&M University.

“Though we haven’t yet made Texas the biotech hub of the world, we have the potential to do so,” she says. “There are people who invest in risky ideas, or crazy ideas, here. There’s a reason they call it being a ‘cowboy.’ ”

Taylor and I spoke about the promise and challenges of innovating in cell regeneration, and how her research into repairing human hearts could help give back to the animals that have made her research possible. Here is an edited version of our conversation:

Xconomy: Of all the organs, why are you focused on the heart?

Doris Taylor: When I was a student, I thought I wanted to study the brain. I was talked into studying muscle by my professor, and once I did, I started studying muscle-nerve interaction. I did my postdoc in New York and that’s when I learned that when you have a heart attack, the heart can’t repair itself. I was learning that and becoming fascinated with the fact that we don’t really have large number of stem cells in the heart that can repair the heart. It made me curious about why. We do in every other muscle. Stem cells can come in and repair the damage.

I moved to Duke Medical, and was talking a lot about kids with MS, and I realized that those kids with MS, they did fine until they were about 10 or 11. They are able to repair themselves until [they are] 5, 6, 8 years old but at a certain point they couldn’t do that anymore. They were running out of cells. That’s like the heart most of the time. You don’t have the cells you need. Maybe you could transplant cells in and restart the repair process. I began my work in the early ’90s and it grew from there.

Understanding that the heart is a muscle just like all the rest of our muscles, and that it didn’t have the cells present for repair, really opened a door for me in terms of understanding how our body repairs itself. For most of our lives, we have stem cells that repair most of our organs and tissues and we use those for most of our lives. As we get older, we no longer have as many and the ones that we have don’t function as well.

X: Why did you decide to come to the Texas Heart Institute last year?

DT: The Texas Heart institute has a long history in regenerative medicine, in either repairing or restoring cardiac function in patients with cardiac diseases. I worked with people at the Texas Heart for the last six years in an NIH research network.

Even though we all believe cell therapy is an important tool in the regenerative medicine arsenal, [there is] a large number of patients with congenital heart disease or with end-stage heart failure for whom cells are probably not going to be enough. So, can we begin to have a bigger solution? To date, we have done a huge amount of work in building artificial and mechanical hearts.

The vision that exists here, if you look at Denton Cooley, Bud Frazier, Billy Cohn, they’re all pioneers. They’ve all been able to realize their vision at THI. There are very few environments where you can do that these days. We have clinicians downstairs, scientists upstairs, patients here and at St. Luke’s where we can really understand what’s needed. The expertise, the level of excellence is what brought me here. And the fact that you really can innovate. It’s a very entrepreneurial community. You can try something important, potentially dangerous but also potentially world changing. You need people who aren’t afraid to dream big, and I’m surrounded by people who think that way every day. I feel like I did 20 years ago when we were having conversations about cell therapy for the first time. If we can imagine it, we can do it.

X: Tell me about the project with Texas A&M.

DT: If you think about it, the vast majority of work we do involves taking a therapy from preclinical studies in animal models of diseases to human studies. But now let’s take everything we learned in humans and make a difference in the non-human veterinary population. Everything we learned about doing cell therapy in humans, we can do for dogs.

It’s exactly the same cardiomyopathy that people get. We’ve partnered with the veterinary school so we have vets who are interested and care very much about this. It’s something that I’ve actually worked with some vets on in the past. There is such an unmet need. People want to keep their pets healthy. We have learned a lot from animal models and it’s nice to be able to apply that to help them.

X: What are your near-term goals?

DT: At the Cell and Organ Biotechnology Center, our goals are to build a heart. Another goal is to identify the people who are at risk for heart disease and develop new methodologies, blood-based tests to tell who’s at risk for a heart attack, to help prevent the onset of heart disease by using cell therapy. We’re validating some diagnostics testing that’s going to be very interesting in the next year to 18 months. I think you’ll see some new blood-based tests that will help us predict who can get better from heart disease, and who can’t, and how we can treat those who have these diseases.

X: What is your biggest obstacle at the moment?

DT: Time is always your biggest obstacle. It keeps going day by day and you can’t rush some treatments. You have to see if they’re going to work for the long term. You can’t make time go faster than it goes. We’re confident that bringing together partners in a number of different disciplines here in the medical center means that we’re well poised to determine the best cells to build different types of therapies. But the stem cell field is not at a place where we can easily get hundreds of billions of beating heart cells that we need to build a whole heart. So creating that capacity something to really focus on.

On the commercialization front, funding for science is at the lowest it’s been in my lifetime in the United States. On the one hand, there is still money from the [National Institutes of Health.] On the other hand, there are large numbers of people who are competing for that money. We’re losing a generation of students, fellows and scientists who don’t understand how to compete in this environment or who don’t want to have to compete in an environment where one in 15 grants is funded. And yet you’re expected to have one or two grants at any given time to support your work. That’s writing 20 grants a year. It’s almost impossible. It’s a difficult environment these days.

There are a huge number of people with ideas, who have IP in those ideas, but don’t have the small amount of money that you need … to take a technology and spin off companies. I’ve talked some with leaders in the medical center, including our new president, and he certainly gets it. We need to have pipelines for ideas to move. I don’t see that happening very rapidly, if at all. If I wanted to start a company tomorrow, if I had the perfect idea and I had intellectual property on that idea, to start a medical device company or biologics company, you need some degree of resources to start that company in this environment where jobs are less secure. People are paying student loans. We’re losing more and more ideas.

X: What is your interaction with the commercialization possibilities of this research?

DT: We’re bringing branches of companies that do cell therapies here. There’s a market here, patients here. I’ve started multiple companies in the past. Yes, we’re close to the science but we also understand that the ultimate goal is a clinical product, a commercial product. We’ve been charged with spinning out multiple companies over the next five years and you’ll see we’re on track to do that. One of those companies is coming on board in the next year. We’ve begun some conversations about the best, first spinoffs. There are a couple of opportunities in the veterinary market and there are also some possibilities in the diagnostic field, where we’ll spin out companies or license out technologies.