Abstract 3176: Molecular Imaging of Mesenchymal Stem Cell Following Myocardial Infarction: Evidence for Transdifferentiation
Background Mesenchymal stem cells (MSCs) hold promise for repairing heart following myocardial infarction (MI) mainly owing to their unique property of transdifferentiating into vascular cells. However, in vivo the transdifferentiation of transplanted MSCs after MI remains controversial. We sought to develop a molecular imaging approach to study the long term fate of transplanted human MSCs after experimental MI in the severe combined immune deficient (SCID) mice.
Methods and Results We constructed a lentivector encoding two sets of double fusion reporter genes, mCherry with renilla-luciferase (RFP-rLuc) and eGFP with firefly-luciferase (GFP-fLuc), driven by a constitutive mscv-LTR promoter or an endothelial specific Tie-2 promoter, respectively. The endothelial specificity of the vector was confirmed by efficient expression of GFP-fLuc in mouse cardiac endothelial cells and human cardiac microvascular endothelial cells, but not in MSCs or HeLa cells. We transducted human MSCs with the lentivector, and then injected 5×105 transducted MSCs into peri-infarct regions of the SCID mouse hearts and tracked the fate of injected cells in vivo by bioluminescence imaging (BLI). The BLI signal derived from rLuc showed that the injected MSCs survived in the peri-infarct areas for longer than 6 weeks. Importantly, the BLI signal from fLuc revealed that MSCs transdifferentiated into endothelial cells 48 hours after injection. Transdifferentiation of MSCs in the peri-infarct region was also confirmed by immunohistochemical analysis.
Conclusions Using a dual-promoter reporter, we demonstrated that human MSCs transdifferentiated into endothelial cells when directly injected into the peri-infarct regions of SCID mouse hearts. Thus, the approach could be powerful means for in vivo identifying the angiogenesis involved in the process of tissue regeneration and/or tumorgenesis.