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

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.