CDU Contributing Editor

A short exposure to a specific combination of two growth factors may be all it takes to stimulate the growth of new blood vessels that persist indefinitely, a new study suggests. Yihai Cao, professor of vascular biology at the Laboratory of Angiogenesis Research at the Karolinska Institute (Stockholm, Sweden), said, "This is what everyone has been hoping for. We have shown that it is possible to grow functional and stable arterial blood vessels in ischemic tissues, which persist in animals for more than a year even once the growth factors have been withdrawn."

Cao and colleagues at Karolinska, together with collaborators in the U.S. and France, reported their findings in a recent issue of Nature Medicine. A patent on use of the combination of growth factors to stimulate angiogenesis has been jointly filed by Cao and his team and Genetix Pharmaceuticals (Cambridge, Massachusetts). They are looking for partners to help develop their work further and finance clinical trials.

Research teams around the world have been focusing for years on ways of stimulating new blood vessels to grow that will improve the blood supply to ischemic tissues. The market for such drugs would be huge, with applications including growing new blood vessels to resupply the heart muscle following myocardial infarction or parts of the brain following a stroke. In conditions where the blood vessels supplying the legs have become blocked, the growth of new blood vessels to supply the ischemic areas could avoid the need for amputation.

Cao said, "Many pharmaceutical companies have developed strategies of injecting a single angiogenic growth factor into the heart or the leg to try to improve blood perfusion. So far, this approach has not been very beneficial, especially for long-term treatments that need to last for months or years. Sometimes, it has even made things worse, with edema of the heart developing because the blood vessels that form are very leaky."

By contrast, he said, during embryonic development the entire vascular tree is exposed to many different growth factors, suggesting that many factors together are needed to grow blood vessels. "We decided to pose the question of whether one growth factor is enough for this process, or do we need more," Cao said. He and his researchers used an experimental system that involves placing a small pellet of a slow-release polymer containing the growth factor or combination of factors that they were testing, inside the corneas of mice. Because the cornea is one of the few organs in the body that has no blood vessels, it is easy to see if new blood vessels grow.

"We found that, on their own, several growth factors could cause blood vessels to grow but that these vessels quickly regressed," Cao said. "It was only when we used the specific combination of platelet-derived growth factor-BB and fibroblast growth factor-2 that we obtained blood vessels that grew faster and remained in the eye for a long time." He added, "to our surprise, we found that these vessels remained even after the growth factors were withdrawn, and some are still present after one year."

They then tested the same growth factors in rat and rabbit models that involve ligating the main artery of the leg, creating ischemia. Again, they found the same combination of growth factors was able to stimulate growth of new arteries. "This is a very good sign for therapeutic angiogenesis," Cao said.

He and his colleagues now want to find out if the combination of platelet-derived growth factor-BB and fibroblast growth factor-2 can reduce ischemia in an animal model of myocardial ischemia, where one of the main blood vessels supplying the heart muscle has been ligated. "Ultimately, we want to know if this strategy brings about useful improvement of heart ischemia following myocardial infarction, and we would like to progress to clinical trials as soon as possible," Cao said.

Charles River showcases Irish facilities

Research tools and services provider Charles River Laboratories (Wilmington, Massachusetts) showcased its new surgical suite/cardiac catheterization lab in County Mayo, Ireland, in early May by hosting a medical device symposium featuring presentations by clinical leaders in cardiology, electrophysiology and orthopedics.

The new facilities are located at the former Biological Laboratories Europe Ltd. facility that was acquired by Charles River Laboratories in June of last year and now operates as Charles River BioLabs. The new surgical facility and cath lab are designed to facilitate research and development studies in the med-tech arena, including device evaluations and safety and efficacy studies.

MediGene spins off cardio unit

MediGene AG (Martinsried, Germany) completed the spin-off of its cardiology and metabolic disease unit by working together with the investment company BioM AG (Munich, Germany) to establish a new firm, Larnax GmbH. MediGene will hold almost 25% of the shares in the new company, which will employ MediGene's cardiology research team of about 25.