Engineered cardiac tissue needs a steady supply of oxygen and nutrients to survive after being grafted onto the heart. In an effort to tackle this problem, researchers from Ben-Gurion University of the Negev, Tel-Aviv University, and Soroka University Medical Center in Israel have developed a method that uses the body as a bioreactor to build working blood vessels in a bioengineered cardiac patch. The results, published this week in the Proceedings of the National Academy of Sciences, represent a crucial step toward generating a bioengineered material capable of repairing damaged heart tissue.
Several labs around the world have been working on ways to engineer living heart tissue by seeding a three-dimensional scaffold with heart muscle cells or with stem cells that can be coaxed into forming these cardiac myocytes. “What they haven’t generally focused on is strategies to create the infrastructure to support these myocytes,” says Frederick Schoen, professor of health sciences and technology at Harvard Medical School and the Brigham and Women’s Hospital. That infrastructure includes blood vessels that bring oxygen to the immigrant myocytes as they try to integrate into the existing heart tissue. Without that vascular support, most of the implanted cells will die.
“In a healthy heart, every single myocyte is flanked by two capillaries,” says Gordana Vunjak-Novakovic, professor of biomedical engineering at Columbia University. In implants without blood vessels, only the outermost cells can grab oxygen. As a result, these patches “look like an M&M candy,” Vunjak-Novakovic says. “Healthy cells on the outside, dead cells on the inside.”
To encourage vascularization in engineered cardiac patches, the Israeli researchers infused a myocyte-seeded scaffold with growth factors that promote cell survival and the growth of new blood vessels. They then implanted each cardiac patch into a living rat’s omentum, the blood-vessel-rich membrane that connects and supports the abdominal organs. Within a week, the patches were populated with mature blood vessels. The researchers then excised the vascularized patches and transplanted them onto the hearts of rats with myocardial infarctions. One month later, the patches appeared not only to survive, but to be well integrated with the animals’ cardiac tissue. The patches improved the rats’ cardiac activity, the myocytes formed muscle fibers that were able to contract, and the researchers could see red blood cells inside the blood vessels, “which means they, too, were fully functional,” says Smadar Cohen, professor of biotechnology engineering at Ben-Gurion University and senior author of the study.