Therapeutic potential of angiogenin modified mesenchymal stem cells: angiogenin improves mesenchymal stem cells survival under hypoxia and enhances vasculogenesis in myocardial infarction.
BACKGROUND
To examine the effects of angiogenin modified mesenchymal stem cells (MSCs) on ventricular remodeling and cardiac function in a rat model of acute myocardial infarction.


METHODS
MSCs were transfected with adenoviral vectors carrying either angiogenin (MSC(AdANG)) or EGFP (MSC(AdEGFP)). Angiogenin gene amplification, protein expression and cell death were assayed after hypoxic treatment. DiI labeled MSC(AdANG) and MSC(AdEGFP) were injected into infracted heart. Six weeks after cell transplantation, echocardiography and histological study were performed.


RESULTS
After hypoxia treatment, angiogenin modified MSCs effectively expressed angiogenin for at least 14 days. The death of MSC(AdANG) was one-third of MSCAd(EGFP), and 50% of untreated MSCs. In the infracted myocardium, the number of DiI labeling cells in MSC(AdANG) group with high angiogenin expression was three-fold that in MSC(AdEGFP) group. Echocardiograms suggested that angiogenin modified MSCs significantly improved left ventricular (LV) systolic and diastolic function. Histological study confirmed that ventricular remodeling was attenuated significantly in MSC(AdANG) group. Furthermore, vasculogenesis was enhanced significantly in MSC(AdANG) group as measured by both factor VIII and alpha-SMA staining.


CONCLUSIONS
Angiogenin modified MSCs enhanced the tolerance of engrafted MSCs to hypoxia injury in vitro and improved their viability in infracted hearts, thus helping preserve the LV contractile function and attenuate LV remodeling through vasculogenesis.
Liu
Xiao-Hong
XH
Institute of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
Bai
Chen-Guang
CG
Xu
Zhi-Yun
ZY
Huang
Sheng-Dong
SD
Yuan
Yang
Y
Gong
De-Jun
DJ
Zhang
Jian-Rong
JR
D000199:Actins / Q000032:analysis; D000256:Adenoviridae / Q000235:genetics; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002196:Capillaries / Q000033:anatomy & histology; D015687:Cell Hypoxia; D002470:Cell Survival / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006684:HLA-DR Antigens / Q000032:analysis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology; D014746:Vimentin / Q000032:analysis
D000199:Actins; D042501:Angiogenic Proteins; D015703:Antigens, CD; D006684:HLA-DR Antigens; D014746:Vimentin; D003094:Collagen; C046366:angiogenin; D012259:Ribonuclease, Pancreatic