title: Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model.
abstract: Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34(+) cells were transplanted to the peri-ischemic zone. To track the in vivo fate of transplanted cells, CD34(+) cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline-treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell-derived, GFP-positive cells were found incorporated into the vascular structure, and GFP-positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34(+) cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell-derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.
authors.affiliation: Center for Molecular Medicine, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Naohide
authors.initials: N
authors.lastname: Ageyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shibata
authors.forename: Takanori
authors.initials: T
authors.lastname: Yasu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Misawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Matsui
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.forename: Uichi
authors.initials: U
authors.lastname: Ikeda
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hanazono
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003331:Coronary Vessels / Q000601:surgery; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006334:Heart Function Tests; D016086:Lentivirus / Q000235:genetics; D008026:Ligation; D008252:Macaca fascicularis; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D003402:Creatine Kinase