Abstract 9991: Mesenchymal Stem Cells Overexpressing CXCR4 (MSC ^CR4 ) Promote Neovascularization as Revealed by Suicide Gene Approach

Background: Our previous studies indicated that MSC CR4 improved cardiac function after myocardial infarction (MI). This study was aimed to investigate the specific role of MSC CR4 in neovascularization of infarcted myocardium using a suicide gene approach. Methods: A regenerating recombinant lentivirus (Lentivector Expression System) was devised to deliver the CXCR4, herpes simplex virus-thymidine kinase (TK) driven by an endothelial-specific promoter of VE-cadherin (pCDH-TK), or without the promoter as negative control (pCDH-null) (Fig. 1A). Ganciclovir (GCV) induced suicide in cells expressing both TK and VE-cadherin. In vitro , pCDH-TK or pCDH-null was transduced into EC (EC TK or EC null ) and cells were treated with vehicle (VEH) or GCV (100µM) for 7 days. In vivo , female rats with myocardial infarction (MI) after permanent LAD ligation were transplanted with either male ordinary MSC (MSC Ord ), MSC (MSC Null ), MSC CR4 or MSC CR4 transduced with pCDH-TK (MSC CR4 -TK). Rats then received VEH or GCV (100mg/kg daily for 7 days) by IP injection before euthanasia. Results: GCV significantly decreased the number of EC TK but had no effect in EC null . Absent GCV, TK expression had no effect on EC growth (Fig. 1B & C). In vivo: GCV reduced significantly neovascularization in post-MI hearts transplanted with MSC CR4 -TK. New vessel formation was not affected either after exposure to VEH or GCV in the absence of pCDH-TK. Y-chromosome positive nuclei were observed in newly formed vessels (Fig. 1D-H). Conclusion: MSC CR4 plays an important role in neovascularization during cardiac repair after infarction.