Congenital heart defects are the most common type of birth defect in the United States, affecting around 1 percent of births each year or around 40,000 babies per year, according to the CDC. Nationwide Children’s Hospital, in Columbus, Ohio is working on improving treatment options for children with congenital heart defects using regenerative medicine. Christopher Breuer, director of the hospital’s Center for Regenerative Medicine, and his colleague Toshiharu Shinoka have developed a tissue-engineered vascular graft (TEVG) specially designed for use in children. Shinoka was the first doctor to implant a TEVG in an infant.

How can regenerative medicine help children with congenital heart defects?

Our focus is on using tissue engineering methods to creating neotissue for use in the reconstruction of complex cardiac anomalies for children that require major congenital cardiac surgery. TEVGs provide a better solution for replacing vessels in children because they use tissues created from the patient’s own cells, and can grow with the patient, rather than having to replace artificial vascular grafts as a child grows. Sometimes surgeons can minimize the number of operations by putting in oversized grafts or delaying surgery, but these come with risks and can cause additional strain on the heart.

How do TEVGs work?

To make a TEVG, we harvest an individual’s own cells and then we seed those cells onto a device that’s called a scaffold, which is a 3-dimensional biodegradable matrix. The scaffold serves to direct the tissue formation. Once implanted in the body, the scaffold begins to dissolve as the new tissue forms. Once the scaffolding is gone, we have a neovessel, which resembles the native blood vessel into which the graft is implanted. The new tissue behaves like a regular blood vessel, including having the ability to grow with the child.

When was the first TEVG implanted in a human?

The first implantation of a TEVG in a human was in Japan in 2001, and the first implantation of a TEVG in the U.S. was in 2011. It was in a three-year-old little girl with a single ventricle cardiac anomaly. She’s now eight years out from her procedure, and she’s still followed by us. She’s doing well. Her graft is growing as she grows.

What challenges remain?

The grafts aren’t without their problems. Some of the patients in our first clinical trial developed narrowing or stenosis of the graft and required treatment with angioplasty. Fortunately, all these patients have subsequently done quite well, and the grafts are growing with the patients. One of the unique things about our laboratory is that we not only go from the bench to the clinic but also go from the clinic back to the bench. When we had this high incidence of early stenosis, we went back to the laboratory and were able to better understand how the tissue forms and causes stenosis. We were able to improve the design of the TEVGs based on the new information we had on how the grafts worked.

What’s the outlook for TEVGs?

There’s always going to be uncertainty when you’re involved in a clinical trial. It’s important to remember that these are experimental, and while we have some very promising data, including clinical data, they are still under investigation, so we’ll have to wait and see. I have found that, in general, patients are quite interested in participating in the trials. There would be great enthusiasm if the trials are successful and if we are able to confirm the growth capacity of the grafts and show good performance.

What are your future goals in regenerative medicine?

We focused on the TEVG as our first attempt at creating a tissue-engineered construct for use in the clinic, but our preclinical work was done in heart valves. There’s a great need for better replacement heart valves for use in congenital heart surgery, so that’s a big focus for our laboratory now. The other thing that we’ve just begun to explore is the application of cardiovascular tissue engineering in the fetal environment. This involves intervening at the fetal stage when the congenital cardiac anomalies are just developing and replacing defective tissues with tissue-engineered constructs. What we’ve discovered is that you can actually implant these tissue-engineered constructs in the fetal environment and since this environment is very plastic there is the potential to reverse some of the cardiac anomalies.

What’s most rewarding about your work?

By far, the greatest joy of research is when you can successfully bring something to the clinic. The patients enrolled in our trial are all incredible children from incredible families, so having the opportunity to work with those families and those patients is extraordinarily rewarding.