Doxorubicin can combat a broad range of cancers, but its use is limited because of severe side effects, particularly heart failure. However, a new study of cardiac stem cells in mice indicates that a brief course of low-dose erythropoietin might reduce the risk of heart failure associated with some anticancer therapies.
The researchers focused on cardiac stem cells in two groups of mice: One set lacked the STAT3 gene in their hearts (STAT3, which drives tumor growth, has been associated with heart failure), and the other was treated with doxorubicin.
Both groups of mice displayed an impaired ability to form new blood vessels essential for oxygen delivery to the heart, and compared with untreated control mice, both groups produced less erythropoietin, a hormone that controls the production of red blood cells. The investigators then demonstrated that erythropoietin binds to cardiac stem cells and is needed to maintain the signaling molecules necessary for production of new blood vessels.
When the mice were given a synthetic erythropoietin derivative at a low dose that did not affect red blood cell production, stem cell differentiation to blood vessel cells was restored and cardiac function was preserved.
“Thus, low-dose [erythropoietin] treatment could potentially be exploited as a therapeutic strategy to reduce the risk of heart failure in certain treatment regimens,” concluded the research team in Cell Stem Cell (2011;9:131-143).