Combinatorial approach for improving the outcome of angiogenic therapy in ischemic tissues.

Two major populations of endothelial progenitor cells (EPC), namely endothelial colony forming cells (ECFC, or late outgrowth EPC) and circulating angiogenic cells (CAC, or early outgrowth EPC) have been reported to play important roles in vasculogenesis in numerous pathological conditions. However, the poor retention of cells into the ischemic tissue and neovessel fragility are two major flaws that need to be overcome for successful angiogenic therapy. The objective of this study was to explore and exploit the functional properties of EPC populations in order to increase the effectiveness of post-ischemic cell therapy. The results indicate different, still complementary, effects of the two EPC populations on adherence and proliferation of vascular endothelial cells. Matrigel plug assay and mouse hind limb ischemia model showed that concomitant administration of CAC-secreted factors and ECFC resulted in three-fold increase in local cell retention and improved muscle perfusion, vessel maturation and hind limb regeneration, in comparison to either treatment alone. By concluding, factors secreted by CAC co-administered at the time of ECFC transplantation improve tissue regeneration and vascular repair through stabilization of newly-derived blood vessels.

Defined-size embryoid bodies formed in the presence of serum replacement increases the efficiency of the cardiac differentiation of mouse embryonic stem cells.

The pluripotent nature of embryonic stem (ES) cells makes them powerful tools in cell replacement therapy for severe degenerative diseases, such as heart failure. However, the development of strategies to increase the efficiency of cardiomyocyte (CMC) differentiation is still needed to produce a sufficient amount of cells for clinical applications. This paper evaluates the impact of the size and the aggregation of embryoid bodies (EBs) on the efficiency of ES cell differentiation into CMCs. ES cells were generated from RAP inbred mice. These cells expressed pluripotency markers and induced teratomas when injected into syngeneic mice, which made them suitable for differentiation into CMCs. We found that the EBs that were formed as a result of in vitro ES cell aggregation generated contractile tissue in direct correlation with the initial number of ES cells. Furthermore, the presence of knock-out serum replacement (KO-SR) during ES cell aggregation resulted in less compacted EBs and increased cell differentiation into CMCs compared to the presence of foetal bovine serum. In conclusion, cardiac differentiation of ES cells is dependent on the size and the degree of compaction of EBs, and the presence of KO-SR during initiation of EBs may lead to improved cardiogenic differentiation of ES cells.