Stem cell studies have been more limited in heart failure than in myocardial infarction (MI). Stefanie Dimmeler (University of Frankfurt, Germany) explains: “The challenges are greater in heart failure since we’re dealing with established scars. These provide a poor substrate for cells when compared to ischaemic/reperfused infarcts which contain islands of surviving cardiomyocytes.”
Promising results...
An additional complication is that, following MI, inflammation within the myocardium attracts stem cells to the tissues, but under the chronic conditions of heart failure these homing capabilities are diminished. Stem cell studies in MI have been contradictory.
However, in heart failure two studies, TOPCARE-CHF and one by Losardo treating patients with intractable MI, have shown promising results (Circulation 2007;115:3165-72). The importance of paracrine effects from stem cells is becoming increasingly clear, including the induction of angiogenesis, the inhibition of apoptosis, and protection from ischaemic-induced injury. This role may be more significant than stem cell proliferation.
BOOST II, reproducing BOOST I benefits to Heart Failure
BOOST II, a multicentre study, is recruiting 200 patients to see whether the positive effects of BOOST I in MI can be reproduced in heart failure. It is also looking to differentiate between cells able to proliferate and secrete factors, and irradiated cells which are unable to proliferate but still able to secrete factors. Principal investigator Helmut Drexler (University of Hannover, Germany), says: “This should answer the key question of whether the beneficial effects of stem cells are produced by paracrine mechanisms rather than by proliferating cells that generate a new myocardium.”
Future studies in heart failure need to look at improving isolation and storage conditions to preserve bone marrow number and function and to produce optimum cell delivery. Studies, such as CELLWAVE by Andreas Zeiher (University of Frankfurt, Germany), are beginning to look at pretreating the heart with ultrasoundguided low energy shock waves. “The hypothesis is that the procedure increases cytokine levels in the heart which augments the homing capacity of subsequently injected cells,” says Dimmeler.