Combining erythropoietin infusion with intramyocardial delivery of bone marrow cells is more effective for cardiac repair.
We postulated that combining erythropoietin (EPO) infusion with bone marrow mesenchymal stem cells (MSC) delivery may give better prognosis in a rat infarcted heart. Acute myocardial infarction (MI) model was developed by coronary artery ligation. Animals were grouped (n=18) to receive intramyocardial injection of 30 microl saline solution without cells (EPO and control groups) or with 3x10(6) MSC from transgenic green fluorescent protein (GFP)+ male mice (MSC and MSC-EPO groups). The animals received either 5000 U/kg body weight EPO (EPO and MSC-EPO groups) or saline solution (MSC and control groups) for 7 days after MI. Cardiac functions were measured by echocardiography and cardiac tissue was harvested for immunohistological studies 3 weeks after surgery. We observed regeneration of MSC in and around the infarcted myocardium in MSC and MSC-EPO groups. Capillary density was markedly enhanced with significantly smaller infarct size and reduced fibrotic area in MSC-EPO group as compared with other three groups. A smaller left ventricular (LV) diastolic dimension and a higher LV fractional shortening were observed in MSC-EPO group than in other three groups. Transplantation of MSC combined with cytokine EPO is superior to either of the monotherapy approach for angiomyogenesis and cardiac function recovery.
Zhang
Dingguo
D
First affiliated hospital of Nanjing Medical university, Nanjing, China.
Zhang
Fumin
F
Zhang
Yuqing
Y
Gao
Xiang
X
Li
Chuanfu
C
Yang
Naiquan
N
Cao
Kejiang
K
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002196:Capillaries / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004452:Echocardiography; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005355:Fibrosis / Q000473:pathology / Q000517:prevention & control; D015552:Injections, Intralesional; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D004921:Erythropoietin