By harvesting a patient’s CD34+ cells from bone marrow, amplifying them, and injecting them directly into the damaged portion of the heart, Losordo says, he is circumventing natural steps that these people’s bodies might not be equipped to perform anymore. In animal studies, he found that the cells were naturally recruited to the heart after an injury to help repair damaged tissue. His research suggests that they secrete growth factors and immune molecules.
“These cells seem to represent one of the natural mechanisms for helping to repair damaged tissue,” he says. “We’re taking a preprogrammed repair mechanism and simply trying to leverage that in patients who have been damaged over the course of many years or decades.”
Lee compliments the thorough nature of Losordo’s work. “I think that this is a promising study, because it was so carefully done and because this patient population can be very incapacitated,” Lee says.
However, he offers three reasons for caution. First, patients in the placebo arm of the study also showed dramatic improvements. Second, although the procedure seemed generally safe, the patients’ hearts released an enzyme that is typically discharged when damage occurs. And third, patients receiving a lower dose of the stem cells fared as well or better than those receiving a higher dose.
“That really implies that we really don’t know what’s going on,” Lee says. “You like to see dose-dependence. If it’s the low-dose [that’s most effective], then you wonder, can we go lower and get the same effect? Have we missed the real benefit?” Other cell therapies for the heart suffer from similar shortcomings, Lee notes.
Losordo expects to start the final phase of clinical trials in a larger group of patients at the end of this year. Trials have already begun using CD34+ cells to help restore blood vessels in people at risk for amputation and in patients with artery blockages in their legs.