Cardioprotective C-kit+ bone marrow cells attenuate apoptosis after acute myocardial infarction in mice-in-vivo assessment with fluorescence molecular imaging

Angelique Ale, Frank Siebenhaar, Katja Kosanke, Michaela Aichler, Karin Radrich, Sina Heydrich, Matthias Schiemann, Isabella Bielicki, Peter B. Noel, Rickmer Braren, Marcus Maurer, Axel K. Walch, Ernst J. Rummeny, Vasilis Ntziachristos, Moritz Wildgruber

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

21 Zitate (Scopus)

Abstract

Cardiomyocyte loss via apoptosis plays a crucial role in ventricular remodeling following myocardial infarction (MI). Cell-based therapy approaches using bone marrow derived c-kit+ pluripotent cells may attenuate apoptosis following ischemic injury. We therefore thought to examine the early course of apoptosis following myocardial infarction - in-vivo - and non-invasively determine the effect of c-kit+ bone marrow cells on post-MI remodeling. We studied apoptosis in wild-type Kit+/+, c-kit mutant KitW/KitW-v and KitW/KitW-v mice after cell therapy with bone-marrow derived c-kit+ cells after ischemia-reperfusion injury. Mice were followed by hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) at 6h, 24h and 7 days after ischemia-reperfusion injury using an Annexin V-based fluorescent nanosensor targeting phosphatidylserine. KitW/KitW-v mice showed increased and prolonged apoptosis compared to control Kit+/+ mice while c-kit cell therapy was able to attenuate the altered apoptosis rates. Increased apoptosis was accompanied by severe decline in heart function, determined by cardiac Magnetic Resonance Imaging, and cell therapy was able to rescue the animals from deleterious heart failure. Post-mortem cryoslicing and immunohistochemistry localized the fluorescence signal of the Annexin V sensor within the infarcted myocardium. Flow cytometry of digested infarct specimens identified apoptotic cardiomyocytes as the major source for the in-vivo Annexin V signal. In-vivo molecular imaging using hybrid FMT-XCT reveals increased cardiomyocyte apoptosis in KitW/KitW-v mice and shows that c-kit+ cardioprotective cells are able to attenuate post-MI apoptosis and rescue mice from progressive heart failure.

OriginalspracheEnglisch
Seiten (von - bis)903-913
Seitenumfang11
FachzeitschriftTheranostics
Jahrgang3
Ausgabenummer11
DOIs
PublikationsstatusVeröffentlicht - 2013

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