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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-03-0685.

Submitted March 5, 2003
Accepted August 14, 2003
Influence of mobilized stem cells on myocardial infarct repair in a nonhuman primate model
Francoise Norol, Pascal Merlet, Richard Isnard, Pascale Sebilion, Nicolas Bonnet, Christian Cailliot, Claire Carrion, Maria Ribeiro, Frederic Charlotte, Pascal Pradeau, Jean-Francois Mayol, Andre Peinnequin, Michel Drouet, Karima Safsafi, Jean-Paul Vernant, and Francis Herodin*
Unite de Therapie Cellulaire, GH Pitie Salpetriere, Paris, France
Service de Biophysique, CHU Mondor, Paris, France
Service de Cardiologie, GH Pitie Salpetriere, Paris, France
Laboratoire de Genetique et d'Insuffisance Cardiaque, GH Pitie Salpetriere, Paris, France
Service de Chirurgie Cardiaque, GH Pitie Salpetriere, Paris, France
Amgen France, Neuilly, France
INSERM, Unite 523, GH Pitie Salpetriere, Paris, France
SHFJ, CEA-DSV, Orsay, France
Laboratoire d'Anatomopathologie, GH Pitie Salpetriere, Paris, France
Institut de Medecine Aerospatiale du Service de Sante des Armees, Bretigny, France
Service d'Hematologie, GH Pitie Salpetriere, Paris, France
Centre de Recherches du Service de Sante des Armees, La Tronche, France
* Corresponding author; email: Francis.Herodin{at}wanadoo.fr.
Although previous findings have suggested that some adult stem cells are pluripotent and could differentiate in an appropriate microenvironment, the fate conversion of adult stem cells is currently being debated. Here, we studied the ability of mobilized stem cells to repair cardiac tissue injury in a nonhuman primate model of acute myocardial infarction. Mobilization was carried out with Stem Cell Factor (SCF), 100 mcg/Kg/Day (D) and Granulocyte Colony Stimulating Factor, (G-CSF), 25 mcg/Kg/D administered 5 days before (D-5 group; n=3) or 4 hours after (H+4 group; n=4) circumflex coronary artery ligation; no growth factor was administered to 3 baboons of the control group. No adverse effect relating to growth factor administration was observed. Flk-1 and transcription factors of cardiac lineages could be detected in peripheral blood only by RT-PCR. When comparing Positron Emission Tomography (PET) with [11C]-Acetate between examinations from D2 and D30, a relative increase (perfusion ratio between infarct and non-infarct regions) of 26% (p=0.01) in myocardial blood flow was found in the H+4 group; the relative rate of oxidative metabolism remained unaltered in the three groups. No change was observed in the echographic indices of the left ventricular (LV) enlargement or systolic function in the three animal groups during the 2 month follow-up. The PET findings concurred with the immunohistochemistry analysis of left ventricular myocardial sections with evidence of endothelial cells but no myocyte differentiation; few cycling cells were observed at this time. Thus, the present data suggests that, in nonhuman primates submitted to coronary artery ligation, mobilization by hematopoietic growth factors could promote angiogenesis in the infarcted myocardium, without detectable myocardial repair.

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