Transplantation of endothelial progenitor cells improves neovascularization and left ventricular function after myocardial infarction in a rat model

2007 ◽  
Vol 103 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Alexander Schuh ◽  
Elisa A. Liehn ◽  
Alexander Sasse ◽  
Mihail Hristov ◽  
Radoslaw Sobota ◽  
...  
Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Andreas Stein ◽  
Antti Saraste ◽  
Marcus Makowski ◽  
Sandra Kühnel ◽  
Elisabeth Weidl ◽  
...  

Background : Experimental studies showed that application of expanded endothelial progenitor cells (eEPC) after myocardial infarction improves cardiac function by enhancing vasculogenesis and by paracrine effects. Erythropoietin beta (EPO) could further improve myocardial function through its anti-apoptotic properties. Methods : Acute myocardial ischemia was induced by ligation of the left anterior descending coronary artery of 23 male athymic nude rats and reperfusion was initiated after 30 minutes. Either 1×10^6 eEPC alone (n=8), 50 IU erythropoietin beta alone (n=7) or eEPC and EPO (n=8) were injected intramyocardially into the border zone of the ischemic area. eEPC were attained by expanding CD34+ cells isolated from cord blood in endothelial medium for 6 –10 passages. A control group did not receive cells or erythropoietin (n=5). After 4 weeks global and regional left ventricular function was measured by MRI in 2- and 4-chamber long-axis series (Philips Achieva MR Scanner). Immunhistology was used to determine vessel densitiy (SMC actin) and infiltrating monocytes (CD68) after 3 days (n=15) and 4 weeks. Results : Global left ventricular function after 4 weeks was higher in rats that received eEPC alone (58±3%, p=.02) or eEPC + EPO (58±6%, p=.01) compared to the control group (54±5%). No changes were found for rats treated with EPO alone (52±4%). Analysis of the regional wall movement showed a further improvement of the movement of the antero-lateral segments only in rats that obtained eEPC + EPO. The number of CD68+ mononuclear cells after 3 days was highest in rats that were treated with eEPC + EPO. This was associated with an increase in vessel density after 4 weeks. In vitro experiments revealed a dose-dependent inhibition of apoptosis by EPO in eEPC. Conclusion: Intramyocardial transplantation of eEPCs + EPO further improved anterolateral wall motion as compared to EPC alone. Improved eEPC survival, alterations in local inflammatory responses and neovascularization may contribute to this effect.


2009 ◽  
Vol 104 (4) ◽  
pp. 403-411 ◽  
Author(s):  
Alexander Schuh ◽  
Elisa A. Liehn ◽  
Alexander Sasse ◽  
Rebekka Schneider ◽  
Sabine Neuss ◽  
...  

2006 ◽  
Vol 13 ◽  
pp. S88
Author(s):  
Sabyasachi Sen ◽  
Juan Merchan ◽  
Jarrod Dean ◽  
Marcia Silver ◽  
Mary Gavin ◽  
...  

2022 ◽  
Vol 12 (4) ◽  
pp. 731-738
Author(s):  
Zhitang Chang ◽  
Guotai Sheng ◽  
Yizhong Zhou ◽  
Zhiyong Wu ◽  
Guobo Xie ◽  
...  

Based on the promotion of myocardial activity via endothelial progenitor cells (EPCs) subsequent to acute myocardial infarction (AMI), our research was designed to explore the influence of excessive HIF-1α expression in expanded EPCs (eEPCs) on promotion of the activity of left ventricle subsequent to MI. Isolation of EPCs from cord blood was performed before transduction with the help of retroviral vector with or without HIF-1α expression. Transplantation was performed subsequent to ligation of the left anterior descending coronary artery in mice. Ejection fraction (EF) of left ventricle was promoted via transplantation after 2 weeks. Excessive HIF-1α expression enhanced EF of left ventricle and decreased the extent of MI. It was revealed via functional studies that excessive HIF-1α expression enhanced proliferation of EPCs triggered by low oxygen concentration and suppressed cell death in the region of infarction. Moreover, markers of endothelium CD31, VEGF, and eNOS were upregulated. Transplantation of eEPCs with excessive HIF-1α expression in AMI can promote myocardial activities by increasing differentiation, generation of vessels, proliferation of eEPCs, and suppressing cell death. The above findings propose that regulation of EPCs via HIF-1α enhances the activity as well as mobilization of EPCs, indicating that reinforcement of expression of HIF-1α is beneficial for coronary heart disease.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Motoo Date ◽  
Hiroshi Ito ◽  
Katsuomi Iwakura ◽  
Atsunori Okamura ◽  
Yasushi Koyama ◽  
...  

Endothelial progenitor cells (EPC) increase after acute myocardial infarction and may contribute to neovascularization in the infarct zone. The aim of this study was to elucidate the relation of EPC release to recovery of microvascualr and myocardial function. Eighteen patients with acute myocardial infarction (AMI) undergoing primary PCI within 12 hours after onset were enrolled. CD34 + cells were counted at days-1, 7 and 14 as an index of EPC. We performed triggered end-systolic myocardial contrast echocardiography (MCE) at every 6 cardiac cycles with continuous infusion of Levovist at days-2 and 14. We performed left ventriculography 6 months later to calculate left ventricular ejection fraction (LVEF) and end-diastolic volume index (LVEDVI). The number of EPC at day-7 was significantly higher than that at day-1 (1.29+/−0.75 vs. 2.10+/−1.25/micL, p<0.001). It was correlated with myocardial blood volume (MBV), that implies microvascular integrity, at day-14 measured from MCE image (r 2 =0.652, p<0.005) and with an increase in MBV from day-1 to day-7 (r 2 =0.533, p<0.005). To evaluate the correlation between EPC and LV function, we divided patients into two groups according to the number of EPC at day-7. LVEF and LVEDVI were comparable between the higher number of EPC and the lower number of EPC groups (49.3+/−12.2 vs. 52.4+/−8.1%, 65.2+/−13.1 vs. 69.1+/−16.6ml/m 2 ). EPC spontaneously released after AMI and number of released EPC is correlated to the amount of neovascularization in the infarct zone. The number of EPC was not necessarily related to the functional improvement or attenuation of LV remodeling.


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