Stem cells save limb damage
Blood vessel blockage, a common condition in old age or diabetes, leads to low blood flow and results in low oxygen, which can kill cells and tissues. Such blockages can require amputation of limbs. Developed therapies that increase blood flow, improve movement and decrease tissue death and the need for amputation.
“In a young, healthy individual, hypoxia—low oxygen levels—triggers the body to make factors that help coordinate the growth of new blood vessels, but this process doesn’t work as well as we age,” said Gregg Semenza, professor of pediatrics and genetic medicine and director of the Vascular Biology Program at the Johns Hopkins Institute for Cell Engineering. “Now, with the help of gene therapy and stem cells, we can help re-activate the body’s response to hypoxia and save limbs.”
People with diabetes have a 40 times higher risk of losing a limb to amputation.
In the current study, the team asked if the same gene therapy treatment could improve reduced blood flow associated with advanced age.
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.
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,” Semenza said. “And that’s critical for bringing such treatment to the clinic.”
The diabetes study was funded by the American Diabetes Association and the Johns Hopkins Institute for Cell Engineering. Authors on the paper are Kakali Sarkar, Karen Fox-Talbot, Charles Steenbergen, Marta Bosch-Marce and Semenza, all of Johns Hopkins.
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