Abstract 11076: Tissue Engineered Complementary Endothelial Progenitor Cell Sheet to Reverse Adverse Ventricular Remodeling Following Ischemic Cardiomyopathy
Introduction Endothelial progenitor cell (EPC) has shown in vitro and in vivo potential therapeutic angiogenesis, while there are still limitations related with improper vascular network. It is essential to optimize mature vessels. We hypothesized that EPC co-cultured with smooth muscle cell (SMC), a component of vascular pericyte, might induce robust and functional vessels, together with enhancing the angiogenic performance and preserving the endothelial-pericyte interaction. Methods and Results Primary EPC and SMC of male Wister rats were isolated and cultured. Expression of VEGF, HGF, TGFβ, and SDF1α in the culture supernatant in vitro was significantly greater in co-cultured EPC with SMC, compared to either EPC- or SMC-only, as assessed by ELISA. No significant difference was found in the concentrations of these cytokines between in the supernatant of “co-cultured” dish of both EPCs and SMCs plated together, and “separate-cultured” dish EPCs and SMCs plated onto the different layers using the trans-well insert, suggesting the importance of a cytokine rich medium. Ischemic cardiomyopathy (ICM) model was generated by inducing myocardial infarction, when co-culturing EPC with SMC was placed onto the heart using either cell-sheet or cell-injection procedure, or a sham operation was performed. Systolic function parameters were greater at 4 weeks after the cell-injection compared to the sham operation, while the cell-sheet yielded further improvement. This finding was consistent with collagen accumulation, capillary density, and importantly, blood perfusion of borderzone area (lectin microangiography) (Table). Conclusions Co-culturing EPC with SMC enhanced the paracrine mechanics, thus inducing well-developed functional blood vessels, lowering fibrosis, attenuating ventricular remodeling, and, consequently, the functional recovery in the rat ICM model with the use of cell-sheet technique, suggesting a possible strategy in the clinical arena.
- © 2012 by American Heart Association, Inc.