But, it was known that when HIF-1 normally activates signals in the body to build new vessels, one of the many types of cells recruited to the site of new vessel growth is a population of stem cells from the bone marrow, which are called bone marrow-derived angiogenic cells. So the team isolated these cells from mice and grew them under special conditions that would turn on HIF-1 in these cells.

When the researchers treated the mice with both the HIF-1 virus and simultaneously injected bone marrow-derived angiogenic cells, treated, older mice were less likely to lose their legs compared to their untreated counterparts.

Further study of these mice showed that activating HIF-1 in the cells appeared to turn on a number of genes that help these cells not only home to the ischemic limb, but to stay there once they arrive. To figure out how the cells stay where they're needed, the research team built a tiny microfluidic chamber and tested the cells' ability to stay stuck with fluid flowing around them at rates mimicking the flow of blood through vessels in the body. They found that cells under low oxygen conditions were better able to stay stuck only if those same cells had HIF-1 turned on.

"Our results are promising because they show that a combination of gene and cell therapy can improve the outcome in the case of critical limb ischemia associated with aging or diabetes," says Semenza. "And that's critical for bringing such treatment to the clinic."

Source: Johns Hopkins Medical Institutions