Intrakoronare Applikation von autologen adulten Stammzellen aus dem subkutanen Fettgewebe: Erste Erfahrungen mit einem Infarktmodell beim Schwein

Abstract

Background: Transplantation of adult autologous stem cells is considered a promising approach for cardiac regeneration after myocardial infarction (MI). The aim of this study was to design an infarct model in pigs and to determine the effect of adipose derived stem cells (ADCs) in pigs following acute MI. Methods: MI was induced in 17 pigs (33±5 kg, ADC animals n=8, control n=7) by occlusion of the mid LAD with an angioplasty balloon for three hours. In the same procedure stem cells were harvested from subcutaneous fat tissue and processed. After reperfusion a cell suspension containing the ADCs (1.5 million autologous cells/kg body weight) or control solution was injected through the balloon. Nuclear scan (Gated SPECT, 99mTc-SestaMIBI) was performed immediately and after 4 weeks to assess the global and regional perfusion and function of the left ventricle. During the following 8 weeks the pigs were monitored by an ECG loop recorder, triggering events were recorded, stored and downloaded via telemetry. After 8 weeks the animals underwent programmed ventricular stimulation and the hemodynamic functional measurements, coronary flow measurements and a third nuclear imaging scan were performed. The animals were euthanized, the hearts removed and sliced in 1 cm sections (apex to basis) to investigate the infarct size, wall thickness by planimetry, the fibroses in the border zone and the capillary density. Results: An acute myocardial infarction could be successfully induced in all pigs and was confirmed by changes in ECG and cardiac enzymes. Four animals died from ventricular defibrillation, two animals had developed a stenosis at the former site of balloon placement at 8-week follow up. There were no differentiates in the flow measurement, hemodynamic and laboratory parameters between ADC group and control group. Except 2 animals ventricular fibrillation could be induced in all animals, there were no differentiation between both groups. The wall in the infarct area was significantly thicker in the ADC group compared to the control group as well as in the border zone. The capillary density in the border zone of the ADC group was significantly increased (p≤0.05) compared to the control group. Conclusion: In this study we could performed successful an infarct model in pigs. Major problem has been shown in ventricular fibrillation and occlusion of the LAD independent of cell injection. Further this study shows a positive effect of ADCs on wall thickness and capillary density after acute MI. Our data suggest that subcutaneous adipose tissue exhibits a beneficial effect on vascular density and remodeling and therefore might be a valuable alternative source of cells to improve cardiac regeneration after acute MI.

• Item Type: Thesis (Dissertation, LMU Munich)
• Keywords: myocardial infarction, stem cell, tissue repair, animal model, pig
• Dewey Decimal Classification: 600 Natural sciences and mathematics > 590 Zoological sciences; 600 Natural sciences and mathematics
• Faculties: Faculty of Veterinary Medicine
• Language: German
• Date Accepted: 28. July 2006
• 1. Referee: Hirschberger, Johannes
• Persistent Identifier (URN): urn:nbn:de:bvb:19-61784
• Signature of the printed copy: 0001/UMC 15837