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

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.

Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges

“…anti-inflammatory and antifibrotic effects; stimulate endogenous repair by paracrine signaling (growth factors and microvesicles); 32,87,88 limited capacity for direct tissue replacement [78][79][80] stimulate endogenous repair by paracrine signaling (growth factors and microvesicles); limited capacity for direct tissue replacement 41,48,178 unclear; evidence for direct remuscularization 24,172 or no evidence of remuscularization; 112 evidence for paracrine effects 37,112,169 modulates gene expression Molecular Therapy Vol. 26 No 7 July 2018 1611 www.moleculartherapy.org Review of hematopoietic lineage CD markers (CD45, CD34, CD14, CD19, and HLA-DR); be plastic adherent when maintained under standard culture conditions; and exhibit the ability to form into colony-forming unit fibroblasts (CFU-Fs) and differentiate into osteoblasts, adipocytes, and chondroblasts in vitro.…”

“…Under the proper conditions, MSCs are capable of transdifferentiating into functional cardiomyocytes in vivo and in vitro. [78][79][80] For example, transplantation of human MSCs, expressing a b-galactosidase reporter gene, into immunodeficient mice with experimental myocardial damage resulted in b-galactosidase + cardiomyocytes within the host myocardium, suggestive of cardiomyocyte differentiation of the xenografted MSCs. 81 Similarly, sex-mismatched cell therapy experiments, in porcine models of acute 32 and chronic MI, 82 provide evidence that engrafted male porcine MSCs differentiated into cardiomyocytes within the female host myocardium, as ascertained by co-localization of the Y chromosome with cardiac transcription factors GATA-4, Nkx2.5, and the structural cardiac protein a-sarcomeric actin.…”

Co-transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice

“…Tracking the cells in real-time by using time-lapse systems on living animals would provide more insight into SSC homing and MSC migration. The processes of MSC migration have been studied before by using advanced imaging techniques like bioluminescence [44] and PET-CT scan [45].…”

Multimodality Molecular Imaging of Cardiovascular Disease Based on Nanoprobes

“…Molecular imaging of special receptors [37], apoptosis [38], and transplanted stem cells [39,40] in the infarcted myocardium has been previously performed in vivo with the use of single imaging model based on nanoprobes. Nowadays, with the development of nanotechnology, the combination of MRI with fluorescent imaging is found to be highly promising and desirable in detection and diagnosis of myocardial infarction in vivo.…”