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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4361-4368.
Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-03-0685.
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HEMATOPOIESIS
Influence of mobilized stem cells on myocardial infarct repair in a nonhuman primate model
Françoise Norol,
Pascal Merlet,
Richard Isnard,
Pascale Sebillon,
Nicolas Bonnet,
Christian Cailliot,
Claire Carrion,
Maria Ribeiro,
Frédéric Charlotte,
Pascal Pradeau,
Jean-François Mayol,
André Peinnequin,
Michel Drouet,
Karima Safsafi,
Jean-Paul Vernant, and
Francis Herodin
From the Unité de Thérapie cellulaire, the Service de cardiologie, the Laboratoire de génétique et d'Insuffisance cardiaque (IFR14), the Service de Chirurgie cardiaque, the Inserm U523, the Laboratoire d'anatomopathologie, and the Service d'hématologie, GH Pitié Salpeêtrière, Paris; Service de biophysique, CHU Mondor, Paris XII-AP-HP; Amgen France, Neuilly; Service Hospitalier Frédéric Joliot, CEA-DSV, Orsay; Institut de Médecine Aérospatiale du Service de Santé des Armées, Brétigny; and Centre de Recherches du Service de Santé des Armées, La Tronche, France.
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, 25 mcg/Kg/d (D), and granulocyte-colony-stimulating factor, 100 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 reverse transcriptase-polymerase chain reaction. When comparing positron emission tomography (PET) with [11C]-acetate between examinations from D2 and D30, a relative increase (perfusion ratio between infarct and noninfarct regions) of 26% (P = .01) in myocardial blood flow was found in the H + 4 group; the relative rate of oxidative metabolism remained unaltered in the 3 groups. No change was observed in the echographic indices of the left ventricular enlargement or systolic function in the 3 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 suggest 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. (Blood. 2003;102:4361-4368).
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