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| The Potential Role of Cytoprotective Cytokines in Mediating the Beneficial Effects of Adult Mesenchymal Stem Cells in Ischemia/Reperfusion Injury |
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Back to 86th Annual Meeting Back to Program Outline Objective: The mechanism(s) underlying the beneficial effects of adult mesenchymal stem cells (MSCs) delivered acutely post-MI is poorly understood. One possible explanation is the ability of MSCs to secrete cytokines that can modulate cardiomyocyte survival and function through an autocrine/paracrine mechanism. A microarray analysis of MSCs revealed they express both hepatocyte growth factor (HGF) and stromal-derived factor-1 α (SDF-1 α), which have been implicated in both cytoprotection and stem cell homing. The aim of our study was to directly compare the effects of these cytokines expressed by MSCs (HGF and SDF-1 α) when administered acutely post-MI. Methods: To test this hypothesis, we subjected adult male Lewis rats to a 90-min LAD occlusion followed by reperfusion. Immediately upon reperfusion, collagen microsponges saturated with 1μg of HGF or SDF-1 were placed on the anterior wall. Results: Echocardiographic analysis at 4 weeks post-MI revealed that LV ejection fraction was increased in the HGF treated group compared to the PBS control group (74.2%+1.7 vs 65.4%+1.8; n=6/group; p=0.002). Likewise, LV end diastolic dimension was reduced at 4 weeks in the HGF treated group compared to the PBS control group (7.60mm+0.32 vs 8.52mm+0.23; n=6/group; p=0.008). Invasive hemodynamics also showed an improvement in contractility and relaxation in the HGF treated group compared to PBS control group (+dP/dT: 7552±939 mmHg/s vs 5693±559 mmHg/s, p=0.048; -dP/dT: -8378±860 mmHg/s vs -5950±772 mmHg/s, p=0.033). In contrast, no significant effect on LV function or remodeling was seen in the SDF-1 treated group. To determine the potential mechanism of this effect, infarct size (IFS) at 72 hours was determined by analysis of 2,3,5-Triphenyltetrazolium chloride-stained sections and expressed as a percentage of the left ventricular area. IFS was decreased 4.2-fold in the HGF treated group compared to the PBS control group (6.6%+3.0 vs 27.6%+6.8; HGF n=4, PBS n=3; p=0.024). Conclusions: Delivery of HGF acutely post-MI, reduces infarct size leading to beneficial effects on post-MI LV remodeling. These data suggest that the beneficial effects of acute MSC transplantation may be related, at least in part, to an ability of MSCs to secrete cytoprotective cytokines. Back to 86th Annual Meeting Back to Program Outline |
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