Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction.
BACKGROUND
Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI.


METHODS
Forty-five male Wistar rats were randomized into three groups: MI or control group (n = 15), MI plus cell transplantation (n = 15), and sham group (n = 15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations.


RESULTS
The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart. Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08 +/- 8.10) mmHg vs (30.82 +/- 9.59) mmHg, P < 0.05], increase in +dp/dt(max) [(4.29 +/- 1.27) mmHg/ms vs (3.24 +/- 0.75) mmHg/ms, P < 0.05), and increase in -dp/dt(max) [(3.71 +/- 0.79) mmHg/ms vs (3.00 +/- 0.49) mmHg/ms, P < 0.05] among MI group with hUCBC transplantation when compared with MI/control group. Masson's trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33 +/- 2.69)% vs (11.10 +/- 3.75)%, P < 0.01]. Based on immunostaining of alpha-actin, the numbers of microvessels were significantly (P < 0.01) increased at the boundary of infarction site. Similarly higher mRNA expression of vascular endothelial growth factor (VEGF) 164 and VEGF188 were found at 7- and 28-day post cell transplantation in MI group with hUCBC transplantation when compared with MI/control group.


CONCLUSIONS
Transplanted hUCBC can survive in host myocardium without immunorejection, significantly improve left ventricular remodeling after AMI and promote a higher level of angiogenesis in the infarct zones. All these factors beneficially affect cardiac repair in the setting of MI. Therefore human umbilical cord blood may be potential source for cell-based therapy for AMI.
Hu
Cheng-heng
CH
Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
Wu
Gui-fu
GF
Wang
Xiao-qing
XQ
Yang
Yan-hua
YH
Du
Zhi-min
ZM
He
Xiao-hong
XH
Xiang
Peng
P
D000199:Actins / Q000032:analysis; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D003094:Collagen / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation; D004562:Electrocardiography; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000166:cytology / Q000637:transplantation; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D016277:Ventricular Function, Left / Q000502:physiology*
D000199:Actins; D018952:Antigens, CD34; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen