Experimental Biology and Medicine > Volume 234, Number 2 > Pp. 222-231

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ORIGINAL RESEARCH ARTICLE

Retention of Nanoparticles-Labeled Bone Marrow Mononuclear Cells in the Isolated Ex Vivo Perfused Heart After Myocardial Infarction in Animal Model

Martin Klabusay*1², Peter Scheer², Michael Doubek*, Kristina Rehakova, Petr Coupek and Drahomir Horky

^* Department of Internal Medicine—Hematooncology, University Hospital Brno and Masaryk University, Brno 625 00, Czech Republic; Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Brno 612 42, Czech Republic; Czech Geological Survey, Brno 658 69, Czech Republic; and Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno 662 43, Czech Republic

¹ Department of Internal Medicine—Hematooncology, University Hospital Brno, Jihlavska 20, Brno 625 00, Czech Republic. E-mail: mklabus{at}fnbrno.cz

Cell therapy of myocardial infarction (MI) is under clinical investigation, yet little is known about its underlying mechanism of function. Our aims were to induce a sub-lethal myocardial infarction in a rabbit, to evaluate the abilities of labeled bone marrow mononuclear cells to migrate from the vessel bed into extracellular space of the myocardium, and to evaluate the short-term distribution of cells in the damaged left ventricle. Sub-lethal myocardial infarction was induced in rabbits by ligation of the left coronary vessel branch (in vivo). The Langendorff heart perfusion model (ex vivo) was used in the next phase. The hearts subjected to MI induction were divided into 3 groups (P1–P3), and hearts without MI formed a control group (C). Nanoparticles-labeled bone marrow mononuclear cells were injected into coronary arteries via the aorta. Perfusion after application lasted 2 minutes in the P1 group, 10 minutes in the P2 and C groups, and 25 minutes in the P3 group. The myocardium of the left ventricle was examined histologically, and the numbers of labeled cells in vessels, myocardium, and combined were determined. The numbers of detected cells in the P1 and C groups were significantly lower than in the P2 and P3 groups. In the P2 and P3 groups, the numbers of cells found distally from the ligation were significantly higher than proximally from the ligation site. Bone marrow mononuclear cells labeled with iron oxide nanoparticles proved the ability to migrate in the myocardium interstitium with significantly higher affinity for the tissue damaged by infarction.

Keywords: bone marrow stem cells, myocardial infarction, cellular therapy, Langendorff isolated heart model, iron oxide nanoparticles

² These authors contributed equally to this work.

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