The effects of age, disease state, and granulocyte colony-stimulating factor on progenitor cell count and function in patients undergoing cell therapy for cardiac disease.

The potential of autologous bone marrow (BM)-derived progenitor/stem cell (BMSC) therapy for cardiac repair maybe limited by patient-related factors, such as age and the disease process itself. In this exploratory analysis, we assessed the impact of age, different disease states, and granulocyte colony-stimulating factor (G-CSF) therapy on progenitor cell concentration and function in patients recruited to our clinical trials of BMSC therapy for ischaemic heart failure (IHD), dilated cardiomyopathy (DCM), and acute myocardial infarction (AMI). The concentrations of CD34+ cells and endothelial progenitor cells (EPCs) were measured in the peripheral blood (PB) and BM of 201 patients. Additionally, cell mobilization following G-CSF and the functional capability of CD34+ cells (using a colony-forming unit assay) were assessed. We found that older age was associated with a lower PB CD34+ cell concentration in the whole study group as well as blunting the effect of G-CSF on BMSC mobilization in IHD patients. Nonischaemic heart failure (DCM) was associated with a significantly higher baseline PB CD34+ and EPC concentration compared to IHD. Following G-CSF treatment, the CD34+ cell concentration was greater in the BM compared to PB, however, the PB CD34+ cells appeared to have a greater and improved (compared to baseline) functional potential. Our results suggest treatment with G-CSF improves the functional potential of mobilized circulating progenitor cells compared to those in the BM. Further work is required to determine which source of cells is best for the purposes of cardiac repair following G-CSF therapy.