Influence of mobilized stem cells on myocardial infarct repair in a nonhuman primate model.
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.
Norol
Françoise
F
Centre de Recherches du Service de Santé des Armées, Departement of Radiobiology-Radiohematology Unit, 24 avenue des Maquis du Grésivaudan 38702-La Tronche Cedex France.
Merlet
Pascal
P
Isnard
Richard
R
Sebillon
Pascale
P
Bonnet
Nicolas
N
Cailliot
Christian
C
Carrion
Claire
C
Ribeiro
Maria
M
Charlotte
Frédéric
F
Pradeau
Pascal
P
Mayol
Jean-François
JF
Peinnequin
André
A
Drouet
Michel
M
Safsafi
Karima
K
Vernant
Jean-Paul
JP
Herodin
Francis
F
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D003326:Coronary Circulation; D003331:Coronary Vessels; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005355:Fibrosis; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress; D010215:Papio; D039904:Pluripotent Stem Cells / Q000637:transplantation*; D019089:Stem Cell Factor / Q000494:pharmacology; D014055:Tomography, Emission-Computed; D014463:Ultrasonography
D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor