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

Ale A, Siebenhaar F, Kosanke K, Aichler M, Radrich K, Heydrich S, Schiemann M, Bielicki I, Noel PB, Braren R, Maurer M, Walch AK, Rummeny EJ, Ntziachristos V, Wildgruber M (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Theranostics Ivyspring International Publisher

Book Volume: 3

Pages Range: 903-913

Journal Issue: 11

DOI: 10.7150/thno.5938

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 Kit^W/Kit^W-v and Kit^W/Kit^W-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. Kit^W/Kit^W-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 Kit^W/Kit^W-v mice and shows that c-kit⁺ cardioprotective cells are able to attenuate post-MI apoptosis and rescue mice from progressive heart failure. © Ivyspring International Publisher.

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich

Germany (DE) Charité - Universitätsmedizin Berlin

Germany (DE) Technische Universität München (TUM)

Germany (DE)

How to cite

APA:

Ale, A., Siebenhaar, F., Kosanke, K., Aichler, M., Radrich, K., Heydrich, S.,... Wildgruber, M. (2013). Cardioprotective C-kit+ bone marrow cells attenuate apoptosis after acute myocardial infarction in mice-in-vivo assessment with fluorescence molecular imaging. Theranostics, 3(11), 903-913. https://doi.org/10.7150/thno.5938

MLA:

Ale, Angelique, et al. "Cardioprotective C-kit+ bone marrow cells attenuate apoptosis after acute myocardial infarction in mice-in-vivo assessment with fluorescence molecular imaging." Theranostics 3.11 (2013): 903-913.

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