ESC Congress 2004: Embryonic endothelial progenitor cells help overcome myocardial infarction in pigs

Myocardial infarction, caused by coronary artery occlusion, can lead up to loss of muscle tissue of the heart and functional detriment, even at times where rapid reperfusion strategies like PTCA or thrombolysis are at hand. In the study presented here, we investigated embryonic endothelial progenitor cells as therapy for ischemia reperfusion injury in a large animal model (pig). This model, which induces an infarct of predictable size in a pig heart, was used to test the cardioprotective potential of the embryonic cells, since adult endothelial progenitor cells (EPCs) have been used in similar models with success and are utilized in ongoing patient studies.

Endothelial progenitor cells are cells which are able to differentiate into endothelial cells and replace the inner vascular wall.In this study, we used 5×106 embryonic endothelial progenitor cells, a number relatively modest with respect to the size of the targeted infarct region. To compensate for this modest cell number, we used a regional delivery system, called retroinfusion, which infuses the cells through the vein draining the infarct region. (Previous studies had shown a substantial increase of efficacy using this application mode).
We now found that indeed retroinfusion of 5×106 embryonic EPCs sufficed to reduce infarct size and improve regional myocardial function in the ischemic area. Interestingly, systemic application of the same number of cells had no significant effect, indicating the relevance of the regional application. The superiority of the regional delivery was confirmed in tests using radioactively labeled cells, where retroinfusion yielded a sixfold higher amount of recruited cells in the heart than systemic application.

Currently, embryonic EPCs are an experimental tool trying to investigate the pathways utilized by these cells to protect the ischemic heart. A variety of efforts is underway to characterize the embryonic EPCs further and to potentially enhance their performance. Because of species differences, it is unclear whether a similar approach can be used in patients.

However, a similar cell line might be derived from human embryonic stem cells, and become a helpful tool for ischemia/reperfusion injury of the heart in the future. C Kupatt (Munich, DE)