Comparison of intramyocardial and intravenous routes of delivering bone marrow cells for the treatment of ischemic heart disease: an experimental study.
The implantation of bone marrow cells (BMCs) into ischemic heart after myocardial infarction can induce angiogenesis and improve heart function. We compared the advantages of delivering BMCs intramyocardially and intravenously. An acute myocardial infarction model was created by the ligation of left anterior descending artery in female Dark Agouti rats. The rats were then randomly divided into four treatment groups: one given an intramyocardial injection of phosphate-buffered saline (PBS group), one given an intravenous injection of 2 x 10(7) BMCs from male rats (i.v. group), one given an intramyocardial injection with total of 2 x 10(7) BMCs from male rats at four points in the infarction area (i.m. group), and one given an intravenous injection of 10-fold the number of BMCs from male rats (10xi.v. group). Quantitative analysis of the SRY gene by real-time PCR showed that the survival of BMCs in the infarcted area was significantly higher in the i.m. group than in the i.v. and 10xi.v. groups, 3 days after treatment (p < 0.05), but not thereafter. However, the blood flow in the infarcted myocardium was significantly better in the i.m. and 10xi.v. groups than in the PBS and i.v. groups 14 days after treatment (p < 0.05). Echocardiography showed that the LVEF continued to decrease in the PBS and i.v. groups, but was stable after 3 days in the i.m. and 10xi.v. groups. By 14 days after treatment, the LVEF was significantly higher in the i.m. and 10xi.v. groups than in the PBS and i.v. groups (p < 0.01). Our results showed that BMCs were more effective delivered intramyocardially than intravenously for inducing angiogenesis and repairing injured myocardium.
Hayashi
Masanori
M
Division of Cardiovascular Surgery, Department of Medical Bioregulation, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi, Japan 755-8505.
Li
Tao-Sheng
TS
Ito
Hiroshi
H
Mikamo
Akihito
A
Hamano
Kimikazu
K
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D002196:Capillaries / Q000033:anatomy & histology / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D004195:Disease Models, Animal; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D005260:Female; D024282:Genes, sry / Q000235:genetics; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D017202:Myocardial Ischemia / Q000628:therapy*; D009206:Myocardium / Q000166:cytology; D018919:Neovascularization, Physiologic; D051381:Rats; D012039:Regional Blood Flow / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D014185:Transplantation, Isogeneic / Q000379:methods; D016277:Ventricular Function, Left / Q000502:physiology
D018952:Antigens, CD34