In vivo imaging to monitor differentiation and therapeutic effects of transplanted mesenchymal stem cells in myocardial infarction

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 a-MHC-HSV1-tk-transfected or un-transfected BMSCs-treated MI model. We used F-18-Fluro-deoxyglucose (F-18-FDG) positron emission tomography (PET) to monitor recovery of cardiac function, and F-18-FHBG PET/CT imaging to monitor transplanted BMSCs differentiation 24 h after 18F-FDG imaging. The uptake of F-18-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 F-18-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 a-MHC-HSV1-tk/F-18-FHBG reporter gene and F-18-FDG metabolism imaging could be used to track differentiation of transplanted BMSCs and recovery of cardiac function in MI.