Abstract 9991: Mesenchymal Stem Cells Overexpressing CXCR4 (MSCCR4) Promote Neovascularization as Revealed by Suicide Gene Approach
Background: Our previous studies indicated that MSCCR4 improved cardiac function after myocardial infarction (MI). This study was aimed to investigate the specific role of MSCCR4 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 (ECTK or ECnull) 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 (MSCOrd), MSC (MSCNull), MSCCR4 or MSCCR4 transduced with pCDH-TK (MSCCR4-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 ECTK but had no effect in ECnull. 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 MSCCR4-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: MSCCR4 plays an important role in neovascularization during cardiac repair after infarction.
- © 2011 by American Heart Association, Inc.