Abstract 3488: Mitochondrial Function Predicts Functional Activity of Autologous Bone Marrow-derived Mononuclear Cells Used for Cell Therapy in Patients With CAD
Initial trials suggest that bone marrow-derived mononuclear cells (BMC) augment neovascu-larization after ischemia. In addition to the number as well as the surface marker of the cells, migratory activity seems to play a pivotal role for the success of cell therapy. Invasion capacity correlates with the improvement of neovascularization by the infused cells in a hindlimb ischemia model of nude mice as well as predicts the reduction of infarct size in patients treated with progenitor cells after myocardial infarction. However, measurement of invasion capacity requires several hours and can, therefore, not serve as an instant quality control of the isolated cells. Mitochondrial function plays an important role in progenitor cell function and mitochondrial membrane potential (MP) can be measured quickly and easily. Therefore, the aim of this study was to examine, whether measuring mitochondrial membrane potential can be used as an easy and reproducible test for BMC function. BMC were isolated from 22 patients with CAD and invasion capacity was measured in addition to MP and colony forming capacity. MP was measured with the lipophilic cation 5,5′,6,6′tetrachloro-1,1′,3,3′-tetraethylbenzimidazol-carbocyanine iodide (JC-1) by FACS analysis. BMC of CAD-patients showed a MP of 0.23±0.14 (range from 0.04 to 0.5). Importantly, MP strongly correlated with the basal (r=0.666, p=0.001) as well as the SDF-1 induced invasion capacity of BMC (r=0.499, p=0.018). Moreover, not-invaded BMC had profoundly lower MP compared to the invaded cells of the same individual (0.44±0.14 vs. 0.79±0.31, n=3). In contrast, colony forming activity, a marker of proliferative capacity of hematopoietic progenitor cells, did not correlate with the MP (r=−0.18; p=0.944). This preliminary study demonstrates that the measurement of MP by FACS-analysis in BMC correlates with the invasion capacity of BMC and might be a tool for an easy and quick measurement of functional capacity of BMC. This method could serve as an instant quality control of cell preparations for clinical cell therapy.