Vascular grafts and stem cells

During the reunion scientific symposium Christopher K. Breuer, M.D., assistant professor of surgery and pediatrics, spoke of his journey from the bench to the clinic and back again as he develops tissue-engineered vascular grafts that could help the most vulnerable of heart patients—infants. The most common birth defects in newborns (present in 1 percent of live births) are congenital cardiac anomalies, Breuer said. Traditionally, pediatric surgeons like Breuer used synthetic materials to graft and patch the small ventricles of an infant’s heart. But synthetic materials couldn’t grow with the baby. In fact, synthetic grafts were the main cause of morbidity and mortality incidents after surgery.

Breuer and his team reasoned that if they could build a graft made out of the infant’s own tissue, the graft would grow with the child and be less likely to rupture, split, or tear. Breuer used a scaffold—made out of the same materials used for dissolvable sutures—on which to “seed” or place an infant’s own cells.

Likening the seeding of cells to the salamander’s ability to regenerate its own tail, Breuer said that the natural graft becomes something like a native blood vessel—it can grow with the infant and the infant’s immune system won’t reject it.

The tissue grafts worked in lambs, but the technique wasn’t perfect, the scaffolding dissolved too quickly before the seeded cells could grow. Now Breuer is working with slower dissolving scaffolding on which to place patches. He applied for his own FDA grant (3,000 pages long) and will start a Yale study on infant heart patients, “blue babies,” this August.

The heart isn’t the only place where tissue grafts could save lives. Breuer said studies in rats have shown that whole tissue organs, including lungs, can be seeded and patched with some success.

Breuer’s goal is lofty (he compared it to President John F. Kennedy’s call for a moon landing). Within 10 years he’d like to see tissue-engineered grafts make the final, giant leap to the clinic for good.

The biggest engineering feat in biology. That’s what Haifan Lin, Ph.D., director of the Yale Stem Cell Center, called iPS, or induced pluripotent stem cells during a lecture called “Stem Cells and Regenerative Medicine: Progress and Prospects” at reunion weekend.

Most haven’t heard of iPS (the name, Lin explained, was a riff on iPhone), but many have heard of stem cells—the controversial embryonic stem cells which are harvested from a blastocyst at an early age of fetal development. Those stem cells have been hailed as panacea in research because they are blank slates; they can contribute to different tissues, and they are much more easily cultured than adult stem cells. But they’re also often too controversial to use in research as scientists must get cells from the blastocyst to start a new cell line.

Adult stem cells, which have long been used in therapies like bone marrow transplants, have research value but are tissue-specific and are harder to harvest and “keep alive” in a Petri dish, Lin explained. For years, this was the great divide in stem cell research, but iPS provides scientists at the Yale Stem Cell Center with a “third way.” “What if we take the least capable cell and make it the most capable cell?” asked Lin. That’s what iPS research has achieved by reprogramming, or “erasing,” adult stem cells to produce iPS. They’re no longer tissue-specific, like adult stem cells, and they don’t come from a controversial source. Diseases like cancer, diabetes, and Parkinson’s could all be affected by iPS research.

Lin highlighted the work of many researchers during his presentation, including In-Hyun Park, Ph.D., whose lab actively works on the generation and genetic constitution of iPS cells. Once iPS cells are fully understood on a genetic and epigenetic level, they can be used for drug screening, disease modeling and cell therapy.

Since 2006, when the center had 32 faculty members; it has become home to 64 member labs, making it one of the fastest growing academic research units at Yale. Top researchers are recruited from all over the world, and Lin emphasized that the center works with the goal of making fundamental scientific discoveries in the lab and bringing them to medical practice.