CIRM funds projects seeking to better understand arterial limb disease and to translate those discoveries into new therapies.
Peripheral limb ischemia, most often characterized as hardening of the arteries in the legs, may be present in as much as 20 percent of the population. But in a small fraction, around two million Americans, it has progressed to the point that it causes pain even when resting and threatens to result in amputation due to wounds that refuse to heal because of poor blood circulation. This is called Critical Limb Ischemia (CLI) and has an amputation rate ranging from 10 to 40 percent.
Physicians can often treat CLI with various forms of minimally invasive surgery. They thread a catheter into the artery or vein and use a balloon or stent to push the blockage back against the vessel wall or a laser to vaporize the plaque. But many CLI patients have disease that is too extensive for these procedures to be fully effective, so for the past few years many researchers have searched for ways to coax the patients’ bodies into growing new blood vessels through a process called angiogenesis. More recently researchers have started to investigate the possibility that stem cells could help with this new vessel growth.
Ischemia research did not join the California stem cell agency’s portfolio until May 2012. At that time, CIRM awarded an Early Translation grant to a team proposing to use stem cell science to produce the two types of cells that produce blood vessels: smooth muscle cells and epithelial cells. They plan to transplant those cells into animal models of CLI and watch for vessel growth.
Disease team awards
University of California, Davis
This team plans to use gene modification techniques to insert a gene for a growth factor called VEGF into a type of stem cell found in bone marrow called mesenchymal stem cells (MSC). VEGF, which is known to stimulate blood vessel growth, has been tried as a treatment for CLI in the past with very limited impact, possibly because the protein does not stay where it is needed long enough. By putting the growth factor into MSCs, which naturally home to inflammation like that in the blocked vessels, the Davis team hopes to get local production of VEGF long enough to stimulate sufficient new vessels to be clinically beneficial. They plan to spend the first year completing the animal testing needed to apply to the FDA to begin a phase 1 trial in the second phase of the grant, which would test the safety of the procedure in humans.