Abstract 854: Homing of Fetal Stem Cells to Damaged Maternal Hearts: A Potential Mechanism for Cardiac Repair in Peripartum Cardiomyopathy
Fetal cells enter the maternal circulation during all pregnancies. They may persist in maternal blood and tissues for decades, creating a state of physiologic microchimerism. We hypothesize that fetal stem cells may be associated with a maternal response to cardiac injury and, therefore, might potentially contribute to cardiac recovery noted in peripartum cardiomyopathy. In order to examine whether fetal stem cells cross the placenta and participate in cardiac repair in the maternal heart, we created a mouse model of cardiac injury during pregnancy. We crossed wild-type B6CBA female mice (age 3– 6 months) with male EGFP transgenic mice. The female mice then underwent ligation of the left-anterior descending (LAD) artery in order to induce an anterolateral myocardial infarction (MI) at gestation day 12. Approximately 50% of the embryos were EGFP-positive. 13 experimental females underwent infarction; 9 female pregnant controls did not undergo surgery. Post-partum females were sacrificed at 1 week post-MI (8 experimental, 4 control) or 2 weeks post-MI (5 experimental, 5 control). Genomic DNA was extracted from each total heart. Using primers designed to amplify EGFP and an internal control gene, ApoB, real time PCR was done in triplicate. The ΔΔCt method was used to calculate the relative quantity of EGFP in experimental hearts compared to controls. Unpaired t-test was used to evaluate the ΔCt values generated from the PCR reactions. Experimental hearts harvested at 1 week post-MI contained 4.1 times more EGFP than controls (p=0.0477). Experimental hearts harvested 2 weeks post-MI contained 3.9 times more EGFP than controls (p=0.0312). In a separate group of experimental and control mice, immunofluorescence analysis with confocal microscopy was utilized to detect EGFP-positive cells in ventricular tissue sections of maternal hearts. EGFP-positive cells were noted in infarct zones of experimental maternal hearts only at both 1 and 2 weeks post-MI. At 2 weeks post-MI, EGFP-positive cardiomyocytes were noted in the infarct zones of maternal hearts, implicating differentiation of fetal stem cells to maternal cardiomyocytes. These data implicate fetomaternal stem cell transfer as an important mechanism in the maternal response to myocardial injury.