547 Hypoimmunogeneic HLA I Knockdown Human Embryonic Stem Cells Induce Host Ignorance and Achieve Prolonged Xenogeneic Survival

2011 
been implemented as the main reason for inefficient cell number at the injured site. We found that the addition of a vasodilator, sodium-nitroprusside (SN) prior to IV MSC injection diminishes lung capillary entrapment. Despite SN pre-treatment the homing of exogenous MSCs to the infarct in our murine model of MI was still low. We sought out to determine whether cytokines released by the ischemic myocardium can enhance the recruitment and survival of infused MSC. Methods and Materials: Cytokines released by ischemic myocardium 24 hours after LAD ligations in mice were analysed for their potential to increase MSC migration and proliferation in vitro. Results: Many cytokines were at least 5-fold upregulated during ischemia, however in our in vitro studies only HGF and VEGF proved to promote both MSC proliferation and migration. Coinjection of MSCs and HGF or VEGF at the time of MI significantly increased the number of MSCs in the infarct. Left-ventricle ejection fraction (LVEF) was monitored 6 months after the MI using ECG-triggered contrast Micro-CT imaging. Treatment with IV injected MSC and HGF or VEGF attenuated the progressive decrease in LVEF. Surprisingly, LVEFs of mice that received HGF or VEGF alone, with no cell-based therapy, were similar to those groups that also received MSCs. Conclusions: Thus, our data show that HGF and VEGF attenuate negative LV remodeling after MI and reduce the mechanism of myocardium regeneration by MSC to a pure paracrine effect.
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