Abstract 16171: Combinatorial Therapy of Cell Sheet Implantation With Pedicle Omentum Flap Promotes Angiogenesis and Stabilizes Blood Vessels With Cardiac Function Recovery in Rat Myocardial Infarction Model
Objective: Cell sheet implantation induces angiogenesis for chronic myocardial infarction (MI), though insuf[[Unable to Display Character: ﬁ]]cient blood supply for the cell sheets and instability of newly formed vessels in ischemic territory may limit its therapeutic effects. The omentum (OM), as a source of angiogenesis factors, has been used clinically to promote revascularization and healing of ischemic tissues by modulating the growth of vasculature. We hypothesized that cell sheets implantation combined with OM flap would better promote angiogenesis for the cell sheets and stabilize newly formed vessels in the myocardium than the single treatment, leading to enhanced functional recovery.
Methods: The left coronary artery was ligated in wild-type Lewis rats 2 weeks prior to dividing into the following groups: 1) combined; skeletal myoblasts sheet implantation plus OM flap, 2) sheet only, 3) OM flap only, and 4) sham operation (n=15 each).
Results: The combined group showed greater improvements in ejection fraction up to 12 weeks and functional capacity in an exercise tolerance test, and a greater amount of pericyte-lined endothelial cells (ECs) (Figure), associated with elevated gene expressions of VEGF, Ang 1, PDGF, and VE-cadherin in the peri-infarct myocardium. The parabiotic pairs (GFP-transgenic MI rat receiving cell sheet implantation plus wild-type oriented OM coverage and that reversed) demonstrated that the ECs migrated into the cell sheets not only from the native myocardium but also the OM, resulting in a greater amount of ECs for the cell sheets in the combined than the sheet only group. The vascular communication between the OM and native coronary arteries was also revealed by in vivo angiography via celiac artery in the combined, while not in the OM flap only group.
Conclusions: Cell sheet implantation plus OM flap promoted angiogenesis and stabilized blood vessels with potent functional recovery in a rat MI model, suggesting its promising clinical application for failing hearts.
- © 2013 by American Heart Association, Inc.