Two Yale physician-scientists are creating a living organ from scratch, coaxing cells to form artificial tissue that can be used to repair or replace faulty blood vessels. Christopher K. Breuer, M.D., assistant professor of surgery and pediatrics, and Toshiharu Shinoka, M.D., Ph.D., associate professor and director of pediatric cardiovascular surgery at Yale-New Haven Children’s Hospital, believe their tissue engineering project could lead to the building of more complex organs.
“We figure if you start with blood vessels, that’s going to be the first step in making just about anything,” said Breuer. “Plus, there’s an immediate need for vessels in vascular and cardiovascular surgery.”
Because the blood vessels Breuer and Shinoka have created rely on stem cells from a patient’s own bone marrow, they are not prone to the inflammation or rejection that affects transplanted tissue. And they are living organs that can grow as a child grows.
When a child is born with such defects as a heart with only a single ventricle, doctors first try to form the child’s own tissue into new vessels that can be used as grafts. “But the problem is these children usually require multiple grafts and you never have enough tissue,” said Breuer. Such alternatives as synthetic Gore-Tex grafts may lead to infections and blood clotting, while biological grafts from animals tend to calcify and need replacement.
Breuer and his colleagues designed a scaffold in the shape of a vein with materials used to make absorbable sutures. They then coat the scaffold with bone marrow stem cells. As blood flows through the vein, the stem cells attract cells from elsewhere in the body to form a blood vessel around the scaffolding. As the vessel forms the original matrix dissolves. The resulting vessel can grow over time, and its elasticity matches that of the body’s own blood vessels.
Over the past six years, Shinoka has used the process successfully in 47 children in Japan. The technique works well and the grafts have an excellent safety profile, he said, and no patients have needed replacement of tube grafts. Shinoka and Breuer expect to hear soon about their application to the U.S. Food and Drug Administration to conduct clinical trials of their grafts at Yale, but they also continue to pursue improvements in their techniques.
Breuer said that his next goal is to figure out which chemical in bone marrow is attracting cells to the scaffolding. He hopes to isolate that compound and build it into the matrix to eliminate the intermediate step of drawing bone marrow from each patient. “We would have immediate off-the-shelf availability when a patient needed a graft,” he said.