Regrowing Blood Vessels With a Potent Molecule

Ever since the Nobel Prize for nerve growth factor was awarded more than 30 years ago, researchers have been searching for ways to use growth factor clinically.

University of Pittsburgh Professor Yadong Wang has developed a minimally invasive method of delivering growth factor to regrow blood vessels. His research, which could be used to treat heart disease, the most common cause of death in the Western world, is published this week in the Aug. 1 issue of the journal Proceedings of the National Academy of Sciences.

Wang is a professor in the Department of Bioengineering in Pitt’s Swanson School of Engineering and the Department of Surgery in the University’s School of Medicine. He is also affiliated with the Pitt-UPMC McGowan Institute of Regenerative Medicine (MIRM). His coauthors are Johnny Huard, professor in the Department of Bioengineering and the School of Medicine’s Departments of Orthopaedic Surgery, Molecular Genetics, and Pathology, as well as MIRM; graduate student Hunghao Chu and postdoctoral fellow Jin Gao in the Departments of Bioengineering and Surgery; and Chien-Wen Chen, a Ph.D. candidate in bioengineering and surgery.

When the researchers injected their growth factor compound under the skin of mice, they saw something amazing: New blood vessels grew, and large ones, not just tiny capillaries. “We had structures that resembled arterioles—small arteries that lead to a network of capillaries,” says Wang.

Moreover, the structures stuck around. At least a month later, after only one injection of the growth factor complex, the new blood vessels were still there.

POWERFUL IN SMALL DOSES

In our bodies, growth factors control many different functions, including cell proliferation, migration, and differentiation. There are even growth factors that inhibit growth of certain cell types or cause cell suicide. “They are very potent molecules,” says Wang.

Being so powerful, growth factor is controlled very tightly by the body, which quickly destroys free-floating growth factor. The half-life for most growth factor injected under the skin is half an hour or less—very short-lived.

With this limitation in mind, the researchers investigated ways to use growth factor efficiently. They hit on a molecule called heparin, one of the molecules that bonds growth factor to its receptor on the cell’s surface. When heparin binds to the receptor and the growth factor, it actually increases the activity of growth factor and stabilizes it.

“Our idea was, ‘Let's use heparin as is, without any modification, to stabilize the growth factor and also to present it to the receptor,’ ” says Wang.

But there was only one catch: If you bond heparin to growth factor, the resulting substance is water-soluble. Injected into the body, the complex dissolves within seconds. We are made mostly of water, after all.