Clin Res Cardiol 101, Suppl 1, April 2012

P990 - Increased angiogenesis in infarcted myocardium after cell-therapy doesn’t improve heart function
A. Schuh1, B. Butzbach1, S. Konschalla2, A. Kroh2, C. V. Suschek3, E. Liehn2
1Medizinische Klinik I - Kardiologie, Pneumologie und Angiologie, Universitätsklinikum Aachen, Aachen; 2Institut für Molekulare Herz-Kreislaufforschung, Universitätsklinikum Aachen, Aachen; 3Universitätsklinikum Aachen, Aachen;
Background: Cell-based therapy is considered a novel and potentially new strategy in regenerative medicine. But the efficacy of cell-based therapy has been limited by the poor survival of the transplanted cells in an ischemic environment. The cells go into apoptosis after transplantation and at later time points only few cells were seen in the infarction areas. Therefore we suggested that the inflammation secondary to the transplantation of the cells could be the mechanism of the improved heart function. To verify this hypothesis we transplantated apoptotic bodies, which carried growth factors but are not able to induce an inflammatory reaction.
Methods and results:The apoptotic bodies were injected directly into border zones of infarcted myocardium in rats. Two months after transplantation the rats were sacrificed and ex-vivo experiments with Langendorff were performed. Regular we analyzed also the heart function using echocardiography. Immunohistochemical stainings were also performed. To see the effect of the apoptotic bodies in vitro, we incubated them with cardiomyocytes in hypoxic condition (2% O2). After 3 hours, we add dihydroethidium (DHE) and measured the cells stress by fluorescent microscopy.
The results showed no improved of the pumpfunction in the hearts of transplanted rats in any groups, in echocardiografic examination as well as in isolated perfusion. Immunohistochemical we didn’t found any differences between the infiltrated neutrophils (70±19 cells/mm² control, 59±7 cells/mm² HUVEC, 78±16 cells/mm² EPC, 87±16 cells/mm² fibroblasts) and monocytes (191±36 cells/mm² control, 193±48 cells/mm² HUVEC, 160±33 cells/mm² EPC, 136±16 cells/mm² fibroblasts) in all groups. This data confirm our hypothesis that the transplantation of the apoptotic body is no able to induce inflammation in the myocardium compared with our previous studies. Except this experiment, we found always an increase in inflammatory reaction after cell transplantation in the same conditions.
Surprisingly, we found an increase in angiogenesis in HUVEC (336±51 vessels/mm², p<0.05 vs. control) and EPC (476±54 vessels/mm², p<0.05 vs. control) groups but not in fibroblast group (150±15 vessels/mm², ns compared with control 170±24 vessels/mm²). This pattern was also found in the animals transplantated with the living cells. Our findings disagree with the statement that angiogenesis can induce alone improvement of the cardiac function.
Although the apoptotic bodies contain SDF-1, VEGF and other growth factors, they are not able to protect the cardiomyocytes from hypoxic injury in vitro. The stress induce by apoptotic bodies from EPC (6.61±0.7 DHE+ cells/field, p<0.05 vs. control), HUVEC (5.95±1.5 DHE+ cells/field, p<0.05 vs. control) and fibroblasts (9.74±2.6 DHE+ cells/field, p<0.001 vs. control, p<0.05 vs. HUVEC and EPC groups) was significantly higher as control.
Conclusion: We showed in this study that angiogenesis induce by transplantation of the HUVEC and EPC doesn’t lead to an improvement of the heart function. Since the microspheres, which contain no growth factors, could induce an improvement of the heart function by increases inflammation, as we showed in our previous studies, we affirm that the role of the inflammation in the cell-therapy could be more important as estimated.
Clin Res Cardiol 101, Suppl 1, April 2012
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-012-1100-6