Abstract
IntroductionEarly randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs. This study was designed to quantify and compare whole body and heart cell distribution after intracoronary or peripheral intravenous injection of autologous bone marrow mononuclear cells in a porcine acute myocardial infarction model with late reperfusion.MethodsMyocardial infarction was induced using balloon inflation in the left coronary artery in domestic pigs. At seven days post-myocardial infarction, 1 × 10(8) autologous bone marrow mononuclear cells were labeled with fluorescent marker and/or 99mTc radiotracer, and delivered using intracoronary or peripheral intravenous injection (leg vein).ResultsScintigraphic analyses and Υ-emission radioactivity counting of harvested organs showed a significant cell fraction retained within the heart after intracoronary injection (6 ± 1.7% of injected radioactivity at 24 hours), whereas following peripheral intravenous cell injection, no cardiac homing was observed at 24 hours and cells were mainly detected within the lungs. Importantly, no difference was observed in the percentage of retained cells within the myocardium in the presence or absence of myocardial infarction. Histological evaluation did not show arterial occlusion in both animal groups and confirmed the presence of bone marrow mononuclear cells within the injected myocardium area.ConclusionsIntravenous bone marrow mononuclear cell injection was ineffective to target myocardium. Myocardial cell distribution following intracoronary injection did not depend on myocardial infarction presence, a factor that could be useful for cardiac cell therapy in patients with chronic heart failure of non-ischemic origin or with ischemic myocardium without myocardial infarction.
Highlights
Randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs
*Correspondence: patricia.lemarchand@univ-nantes.fr 1INSERM UMR915, l’institut du thorax, IRT-Université de Nantes, 8 quai Moncousu, BP 70721, Nantes, F-44007 Cedex 1, France Full list of author information is available at the end of the article formal trials, deploying a range of differing cell-based therapies with the shared objective of improving cardiac repair [1]. Most of these initial human trials suggest functional improvement, randomized clinical trials reported contradictory results [2, 3] suggesting that the ideal protocol design still needs to be defined, with the help of large animal models [4]
The 25 surviving animals were randomly assigned to three different groups: five were used as controls (MI without bone marrow-mononuclear cells (BM-MNCs) injection), 16 received intracoronary BM-MNCs, four received intravenous BM-MNCs
Summary
Randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs. This study was designed to quantify and compare whole body and heart cell distribution after intracoronary or peripheral intravenous injection of autologous bone marrow mononuclear cells in a porcine acute myocardial infarction model with late reperfusion. With an experimental design of acute myocardial infarction (MI) and autologous cardiac cell therapy that closely match clinical trials [2, 3] to analyze and quantify whole body and heart distribution of injected autologous bone marrow-mononuclear cells (BM-MNCs). We evaluated the optimal route of delivery (intracoronary versus peripheral intravenous injection)
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