Mesenchymal Stem Cells Combined with Hepatocyte Growth Factor Therapy for Attenuating Ischaemic Myocardial Fibrosis: Assessment using Multimodal Molecular Imaging.
Clinically, myocardial fibrosis is increasingly being recognized as a new therapeutic target for ischaemic heart diseases. The aim of this study was to investigate whether noninvasive multimodal molecular imaging could be used to dynamically assess whether the combination of bone marrow mesenchymal stem cells (BMSCs) and hepatocyte growth factor (HGF) therapy can synergistically attenuate myocardial fibrosis after myocardial infarction (MI). MI was induced in 28 rats by coronary ligation with subsequent injection of BMSCs/HGF, BMSCs, HGF, or saline into the border zone under echocardiography guidance. The therapeutic procedure and treatment effects were tracked and assessed using bioluminescence imaging (BLI) and cardiac magnetic resonance (MR) imaging. Four weeks after transplantation therapy, cardiac MR imaging demonstrated that BMSC/HGF-treated animals showed better ejection fractions (p < 0.001) and smaller scar sizes (p < 0.001) than those treated with BMSCs or HGF alone. Histopathological and immunohistochemical results showed less collagen deposition, increased microvessel densities and more regenerative cardiomyocytes in the BMSC/HGF-treated animals than in those receiving HGF or BMSCs alone (all p < 0.05). Multimodal molecular imaging allows a specific and timely strategy to be established for dynamically tracking treatment and noninvasively assessing the therapeutic effects. Under echocardiography guidance, intramyocardial injection of transfected HGF with BMSCs can enhance cell survival, improve cardiac function, stimulate angiogenesis, and reduce myocardial fibrosis in a post-MI rat model.
Department of Radiology, Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, China.
Huizhu
H
Chen
Department of Radiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China.
Rui
R
Xia
Department of Radiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China.
Zhenlin
Z
Li
Department of Radiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China.
Lizhi
L
Zhang
Department of Radiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China.
Chunchao
C
Xia
National Engineering Research Center for Biomaterials, Sichuan University, China.
Hua
H
Ai
Department of Radiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China.
Zhigang
Z
Yang
Department of Radiology, Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, China.
Yingkun
Y
Guo
D064591:Allografts; D000818:Animals; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
D017228:Hepatocyte Growth Factor