Abstract
Here, we used a noninvasive multimodality imaging approach to monitor differentiation of transplanted bone marrow mesenchymal stem cells (BMSCs) and recovery of cardiac function in an in vivo model of myocardial infarction (MI). We established a rat MI model by coronary artery ligation. Ninety rats were randomly assigned into four groups: sham-operated, MI model, and α-MHC-HSV1-tk-transfected or un-transfected BMSCs-treated MI model. We used 18F-Fluro-deoxyglucose (18F-FDG) positron emission tomography (PET) to monitor recovery of cardiac function, and 18F-FHBG PET/CT imaging to monitor transplanted BMSCs differentiation 24 h after 18F-FDG imaging. The uptake of 18F-FDG at 3, 16, 30 and 45 days after BMSCs injection was 0.39 ± 0.03, 0.57 ± 0.05, 0.59 ± 0.04, and 0.71 ± 0.05% ID/g, respectively. Uptake of 18F-FHBG increased significantly in large areas in the BMSCs-treated group over time. Ex vivo experiments indicated that expression of the cardiomyocyte markers GATA-4 and cardiac troponin I markedly increased in the BMSCs-treated group. Additionally, immunohistochemistry revealed that HSV-tk-labelled BMSCs-derived cells were positive for cardiac troponin I. Multimodal imaging systems combining an α-MHC-HSV1-tk/18F-FHBG reporter gene and 18F-FDG metabolism imaging could be used to track differentiation of transplanted BMSCs and recovery of cardiac function in MI.
Highlights
Ischaemic heart disease is a serious threat to human health, and stem cell transplantation may be an effective treatment[1, 2]
Animal models and general conditions. 90 rats were assigned into four groups before surgery: sham-operated (G1), myocardial infarction (MI) model (G2), and α-myosin heavy chain (α-MHC)-herpes simplex virus type 1 thymidine kinase (HSV1-tk)-transfected bone marrow mesenchymal stem cells (BMSCs)-treated MI model (G3), BMSCs-treated MI model (G4)
The results indicate that the transplanted BMSCs differentiated to cardiomyocytes after α-MHC-HSV1-tk-transfected-BMSCs injections
Summary
Ischaemic heart disease is a serious threat to human health, and stem cell transplantation may be an effective treatment[1, 2]. Recent studies have demonstrated that BMSCs exhibit self-renewal and multipotency, and they are considered ideal progenitor cells for stem cell transplantation[3,4,5]. They are obtained and cultured, and express exogenous genes efficiently. We generated stable α-MHC-HSV1-tk-expressing cell lines by lentiviral transduction of BMSCs. Taken together, our findings establish a multimodality imaging approach for monitoring differentiation changes and therapeutic effects of transplanted BMSCs and VEGF for the treatment of MI in vivo
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