Influence of angiogenesis by implantation of bone marrow mononuclear cells in the rat ischemic heart.
Bone marrow implantation (BMI) enhances angiogenesis in several animal models of ischemic diseases, and it is currently applied in the clinical treatment of humans. However, the mechanisms of this effect have not yet been fully described. Rat bone marrow mononuclear cells (BM-MNCs) were obtained by Histopaque density gradient centrifugation and injected directly into the ischemic myocardium of the test rats (BMI group), which were then examined and compared with the groups that received surgery only (Controls) or surgery and an injection of phosphate buffered saline (PBS group). Cardiac function was evaluated by echocardiography, and neovascularization was examined both histologically and immunohistochemically before, 1 day after, and 7 or 28 days after the operation. BM-MNCs were analyzed by fluorescence staining for the endothelial cell marker CD31 and alkaline phosphatase (ALP). The mechanisms of angiogenesis were examined by gene expression analysis. In the BMI group, cardiac function parameters at 7 days after operation were significantly improved and the number of capillaries in the myocardium was significantly larger than that in the PBS and Control groups. Gene analysis showed the expression of 12 genes in the BMI group 7 days after operation. The implantation of BM-MNCs into the myocardiumin cases of acute infarction enhances cytoprotection and angiogenesis by affecting gene expression.
Yokokura
Yoshinori
Y
Department of Surgery, Kurume University School of Medicine, Kurume, Japan. ynoriy@med.kurume-u.ac.jp
Hayashida
Nobuhiko
N
Okazaki
Teiji
T
Nakamura
Eiji
E
Tayama
Eiki
E
Akashi
Hidetoshi
H
Aoyagi
Shigeaki
S
D000818:Animals; D016026:Bone Marrow Transplantation; D007150:Immunohistochemistry; D008297:Male; D009000:Monocytes / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000601:surgery*; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew