ObjectiveOur objective was to determine whether autologous endothelial progenitor cells (EPCs) delivered into the pericardial space will migrate to and incorporate into ischemic myocardium in a porcine model.Background
Use of EPCs to enhance neovascularization and preserve myocardial function in ischemic tissue is undergoing intense scrutiny as a potential therapy. Delivery into the pericardial sac may overcome some of the limitations of currently employed cell delivery techniques.
Methods
EPCs were immunopurified from peripheral blood of Yorkshire pigs by selecting for the CD31 surface antigen, and adherent cells were cultured for 3–5 days. After myocardial ischemia was induced in the left anterior descending (LAD) artery, either autologous DiI (1,1′-dioctadecyl-1-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)-labeled EPCs (n=10) or serum-free medium (SFM; n=8) was delivered into the pericardial space using a percutaneous transatrial approach. Animals were sacrificed on Day 7 or 21. Echocardiography was performed at baseline, during ischemia, and on Day 7 in six SFM group animals and six EPC group animals.
Results
On Day 7, EPCs were identified in the left ventricular (LV) anterior wall or anterior septum in all six EPC-treated animals (cell density of 626±122/mm2). On Day 21, EPCs were identified in the LV anterior wall or anterior septum in three of four EPC-treated animals (cell density of 267±167/mm2). These cells showed dual staining for DiI and Bandeiraea simplicifolia lectin I (a marker of both native and exogenous endothelial cells). At the Day 7 follow-up, echocardiography demonstrated that fractional shortening in the EPC-treated group was 30.6±3.4, compared with 22.6±2.8 in SFM controls (P=.05).
Conclusions
EPCs can migrate from the pericardial space to incorporate exclusively into areas of ischemic myocardium and may have favorable effects on LV function.
