The body is a lot like a city. The immune and gastrointestinal systems collaborate to protect us and transport food, for example. But the circulatory system is the superhighway that keeps the entire enterprise running. When cardiovascular disease constricts blood vessels, oxygen and nutrients have trouble reaching their destinations and cells die.

This is what happens during peripheral artery disease (PAD), in which arterial plaque blocks vessels in the legs. The condition can cause pain, skin breakdown and even gangrene. In extreme cases, limbs must be amputated.

An internationally renowned interventional cardiologist, John Laird has seen more than his share of PAD. The rise of type 2 diabetes and persistent smoking have made the condition increasingly common. For patients with less severe cases, the disease can be treated with exercise, medications, angioplasty or bypass. Some aren’t so lucky.

“Our goal is to help patients with peripheral artery disease who are at greatest risk for losing their legs,” says Laird, medical director of the UC Davis Health System Vascular Center. “In many cases, these are desperate patients with no other options. Amputation is often the beginning of a downward spiral toward losing the other leg and possibly worse.”

Making new blood vessels

One of the most promising approaches to PAD may be to harness angiogenesis, the process by which the body grows new blood vessels. By delivering proteins called growth factors that spur angiogenesis, such as Vascular Endothelial Growth Factor (VEGF), Laird and colleagues hope to convince the body to grow new vessels, creating biological bypasses that help blood flow more freely. But like many promising ideas, there were kinks to work out.

“There was a lot of initial promise with growth factors, but the promise wasn’t realized because these factors just didn’t stick around long enough and in the right concentrations,” says Laird.

In other words, what they needed was a VEGF factory that could supply a continuous stream of growth factors to create new blood vessels. Fortunately, the expertise to build such a factory exists at UC Davis.

A fruitful collaboration

For help, Laird turned to Jan Nolta, who directs the UC Davis Stem Cell Program. Stem cells were a logical choice, as they already produce many growth factors. Equally important, stem cells can be injected into a limb and will remain where they are deposited.

To enhance the therapeutic effect even further, the Nolta lab engineered adult mesenchymal stem cells (MSCs), isolated from bone marrow, to produce enhanced levels of therapeutic growth factor.

“MSCs produce a nice array of factors, which can help damaged cells, but we are specifically engineering them to produce VEGF, the most potent one,” says Nolta. “We’ve been working on this approach with John Laird and other clinicians for six years, and this combination of clinical and scientific expertise is translating bench science into a new therapy.”

Though it has been a slow, painstaking process, their work, which has been funded by the California Institute of Regenerative Medicine, is poised to bear fruit for patients. Therapeutic angiogenesis is currently in preclinical studies. The team plans to begin enrolling patients for clinical trials in early 2015, after approval from the FDA can be obtained.

“This has been a wonderful partnership between the Vascular Center and the Stem Cell Program,” says Laird. “Now we have a really good chance of helping patients with limb-threatening PAD who lack other good options.”