Research
Cell distribution after intracoronary bone marrow stem cell delivery in damaged and undamaged myocardium: implications for clinical trials
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* Corresponding author: Patricia F Lemarchand patricia.lemarchand@univ-nantes.fr
1 INSERM UMR915, l'institut du thorax, IRT-Université de Nantes, 8 quai Moncousu, BP 70721, Nantes, F-44007 Cedex 1, France
2 Université de Nantes, Faculté de Médecine, Institut Fédératif de Recherche Thérapeutique 26 (IFR26), 8 quai Moncousu, BP 70721, Nantes, F-44007 Cedex 1, France
3 CHU Nantes, l'institut du thorax, Hôpital Nord Laënnec, Boulevard Jacques Monod, Nantes, F-44093 Cedex 1, France
4 Animal Pathophysiology and Functional Pharmacology Unit (UPSP 5304), Ecole Nationale Vétérinaire de Nantes, Atlanpole La Chantrerie, Nantes, F-44307 Cedex 3, France
5 CHU Nantes, Service d'Anatomo-pathologie, Hôpital Nord Laënnec, Boulevard Jacques Monod, Nantes, F-44093 Cedex 1, France
6 INSERM U957, Laboratoire de Physiopathologie de Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine 1, rue Gaston Veil, Nantes, F-44035 Cedex 1, France
Stem Cell Research & Therapy 2010, 1:4 doi:10.1186/scrt4
Published: 15 March 2010Abstract
Introduction
Early 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.
Methods
Myocardial 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).
Results
Scintigraphic 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.
Conclusions
Intravenous 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.