Backgrounds: Most studies of cellular cardiomyoplasty were focused on stem cells including human BM-derived Mesenchymal Stem cells (hMSC) & endothelial progenitor cells (hEPC). Previously we have reported the potential of HUVEC to undergo rat cardiomyocytes (CMC) differentation. However, 'homing’ and the long-term survival of these human cells in a rat were not known. Therefore, we investigated the presence of 'homing’ of these human cells (hMSC, hEPC, HUVEC), and the effect of systemic delivered hMSC for functional improvement in a rat model of MI. Method: 3 type cells (hMSC, hEPC, HUVEC) were labeled wth DAPI. 5×106cells (labeled with DAPI) were injected into the femoral vein at reperfusion time in a rat model of MI(n=9). MI was induced by 5-hours coronary ligation followed by reperfusion. The hearts including other organs were harvested at 1, 4weeks after MI, and the human cells were evaluated by 3-D image analysis. Functional improvement was evaluated by echocardiography and LVEDP at 4 weeks after systemic delivered hMSCs (n=3, control MI: n=3) after MI. Result: 1) Many hMSC-DAPI(+) cells were detected and survived at infarct border zone & infarct zone upto 4 weeks after MI (n=3), Some hEPC-DAPI (+) cells were detected at infarct and infarct border zone at 1 week, but not detected at 4 weeks after MI (n=3). HUVEC-DAPI(+) cells were not detected in the heart at 1, 4 weeks (n=3). 3 types of DAPI(+) cells were observed at the lung, brain, liver & kidney at 1 week, but not observed at 4weeks after MI. Only hMSC-DAPI(+) cells were observed at heart and lung. In systemic delivered hMSCs after MI, LV fractional shortening at 2 weeks (control vs hMSC; 13.0±2.1 vs 24.0±11.5%) was increased and LVEDP was much improved after 4 weeks later (1 week vs 4 weeks; 18.5± 13.4 vs 9.6±2.9mmHg). Conclusion: Despite of different species, systemic venous delivered hMSCs were engrafted and successfully survived at infarct border zone upto 4 weeks in rat MI. This study shows the presence of ‘homing’ and ‘immunotolerance’ of hMSC to rat and functional improvement of systemic venous delivered hMSCs
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