title: Cardioprotective C-kit⁺ bone marrow cells attenuate apoptosis after acute myocardial infarction in mice - in-vivo assessment with fluorescence molecular imaging.
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.
authors: 1. Institute for Biological and Medical Imaging, Helmholtz Zentrum München and Technische Universität München, Germany.
authors: Angelique
authors: A
authors: Ale
authors: Frank
authors: F
authors: Siebenhaar
authors: Katja
authors: K
authors: Kosanke
authors: Michaela
authors: M
authors: Aichler
authors: Karin
authors: K
authors: Radrich
authors: Sina
authors: S
authors: Heydrich
authors: Matthias
authors: M
authors: Schiemann
authors: Isabella
authors: I
authors: Bielicki
authors: Peter B
authors: PB
authors: Noel
authors: Rickmer
authors: R
authors: Braren
authors: Marcus
authors: M
authors: Maurer
authors: Axel K
authors: AK
authors: Walch
authors: Ernst J
authors: EJ
authors: Rummeny
authors: Vasilis
authors: V
authors: Ntziachristos
authors: Moritz
authors: M
authors: Wildgruber
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000737:chemistry / Q000502:physiology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D008279:Magnetic Resonance Imaging; D051379:Mice; D057054:Molecular Imaging; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D061848:Optical Imaging; D039904:Pluripotent Stem Cells / Q000737:chemistry / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D014057:Tomography, X-Ray Computed
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: apoptosis; heart failure; imaging; infarction; reperfusion.