Using Patients' Own Stem Cells to Combat PAD
Despite leading healthy and active lives, both were recently diagnosed with a severe form of peripheral artery disease (PAD) called critical limb ischemia (CLI). Both were referred to Dartmouth-Hitchcock's highly-regarded Vascular Surgery Program and have been cared for by leading vascular surgeons Richard Powell, MD, and Daniel Walsh, MD. And like many other patients with CLI, they were at high risk for a lower leg amputation.
"PAD is very similar to heart disease and is caused by blockages due to atherosclerosis or hardening of the arteries, except it occurs in the leg arteries," explains Powell. "Major risk factors include smoking, diabetes, high cholesterol, and family history. In the US, about 9½ million patients have lower extremity PAD. Of those, about 10 percent—or 1.5 million—suffer from CLI which causes symptoms that can be very disabling to patients."
For Hugo, an avid runner, those symptoms included pain and swelling of his right foot, as well as a non-healing ulcer on his fourth toe. "I was shocked when I first learned that I had PAD, because I'd taken such good care of myself," says Hugo, who was diagnosed with type 1 diabetes at age 23 but had successfully managed his disease with medication (insulin), watched his diet, and exercised regularly. "My doctors explained that even well-managed diabetes can cause damage over time, but we hoped that my healthy lifestyle might allow therapies to work.
"I used to run five miles a day, and I kept running after my problems started because that's when my foot felt best, due to the increased blood flow," continues Hugo. "But within 20 minutes of stopping, the foot would swell right back up. It was hard to get a shoe on and the walking was murderous. It just got worse and worse over time, to the point where it also made sleeping very difficult—I've had to keep my right foot planted on the floor during the night to stop the nerve pains."
Irene's symptoms also affected her sleep. "I had awful twinges in my leg," she recalls. "It eventually went away, but it did keep me awake many nights. My troubles began with walking. I really enjoyed taking a long walk every day, but started experiencing sharp pains in my calf. If I stopped, it went away. I tolerated it for a while, but it started happening more and more frequently. At one point, I remember having to climb stairs and feeling like I was going to pass out from the pain. The doctors were surprised to find a blockage between my groin and knee since the only risk factor I had was elevated cholesterol, which I had controlled well with medication."
A novel treatment option
Dartmouth-Hitchcock's world-class vascular surgery team offers a wide range of options that can effectively individualize care for each patient based on their medical problems, the severity of their disease, and the anatomy of where their blockages are, says Walsh. "For patients with CLI," he explains, "it basically boils down to two general approaches—angioplasty, where we use certain devices to clear plaque out and prop the artery open, or by-pass surgery, where we use a patient's vein or a piece of plastic graft to go around the blockage."
Hugo and Irene each underwent both kinds of interventions, but they only worked temporarily. That placed them in a relatively small set of patients nationally—about 150,000—who have no other options for restoring blood flow to their lower extremities. Or so they thought. "It turns out that we have one of the leading experts in the U.S.—Dr. Powell—in stem cell research related to revascularization," says Walsh. "It involves literally growing new blood vessels to create new blood flow to save dying limbs. And it's really focused on trying to help patients like Hugo and Irene."
Irene decided to enroll in a phase-II clinical trial being led by Powell that involved removing bone marrow from patients' hips, isolating and growing stem cells from it, and injecting the stem cells into the ischemic areas (in about 20 different spots) of the patients' legs and feet. Later, Hugo chose a similar treatment option, though not as a trial participant. "The study was blinded and included a placebo group, so no one knew until afterward who received the actual treatment and who received a placebo," says Powell. "What we found was very encouraging—the patients who received the stem cells had a significantly lower incidence of amputation, wound worsening, or death when compared to the placebo-treated patients."
The results were so promising, in fact, that Powell is now leading a third and final phase of the trial, begun in January, which includes 550 patients in 80 centers across the U.S. "If this study has similar results, in all likelihood it will be approved for use by the FDA, and that's very exciting," he says. "You know, I'm a bit of a skeptic about these things, but I'm very impressed by what these stem cells can do. When they're placed in a low-oxygen environment, they transform to become more vascular in orientation, and they also release various growth factors that are important in wound healing."
Hope for CLI patients
It didn't take long for Irene to know, or at least strongly suspect, that she'd received actual stem cells in the trial. "I'm just so very grateful that I was part of the trial," says Irene, who adds that her care team, led by Study Coordinator Olga Sobko, RN, and Dr. Walsh, "has been wonderful to deal with."
"My condition was getting very serious at the time; had I chosen not to do anything, I would have lost my foot," she says. "The trial was an easy process to go through and they made sure I was comfortable through the procedures. Now, I'm back to being active. And although I still can't do longer walks, I'm able to do the things that I enjoy like shopping, housework, and sewing. And best of all, I can still take care of myself."
While Hugo's fourth toe eventually had to be removed, his foot has continued to improve, especially after a second set of injections at the base of his toes, and the nighttime nerve pain is getting better. "I'm back to bicycling 45 minutes a day and the foot feels very good," he says. "It's too early to tell if this is going to work long term, but I'm very encouraged. The care I've received from Dr. Powell and my care team has really been special. I've been to many hospitals all over the U.S. (as a diabetic) and this is by far the best experience I've had."