Abstract 11074: Addition of Mesenchymal Stem Cells Enhances the Therapeutic Effects of Skeletal Myoblast Cell-Sheet Transplantation in a Rat Ischemic Cardiomyopathy Model
Introduction: The use of cell sheets for transplanting skeletal myoblasts (SMBs) into the heart has been shown to effectively deliver functional SMBs, thereby inducing a functional recovery of ischemic cardiomyopathy (ICM) in a paracrine manner. However, magnitude of the therapeutic effects is limited by the potential ischemia of the transplanted cell sheet. Mesenchymal stem cells (MSC) have been shown to have pro-survival/proliferation and anti-apoptotic effects on co-cultured cells in-vitro. We therefore hypothesized that the addition of MSC to SMB cell sheets may enhance the survival of transplanted SMBs and the therapeutic effects in ICM.
Methods and Results: Co-cultured cell sheets, cell sheets of primary SMBs of male Lewis rats (r-SMB), and cell sheets of primary MSCs of human female subcutaneous fat tissues (h-MSC) were generated by culturing r-SMB and h-MSC in temperature-responsive dishes. Among many candidate mediators of paracrine effects, expression of HGF and VEGF of rat origin in vitro was significantly greater in the co-cultured cell-sheet compared to the r-SMB sheet, as assessed by both real-time PCR and ELISA. ICM model was generated by occluding left coronary artery in female athymic nude rats for 2 weeks, when co-cultured cell sheets, r-SMB cell sheets, or h-MSC cell sheets were implanted or a sham operation was performed (n=10 in each). Systolic and diastolic function parameters were greater at 8 weeks after the either single cell-sheet implantation compared to the sham operation, while the co-cultured cell-sheet yielded further improvement. This finding was consistent with capillary density, collagen accumulation, myocyte hypertrophy, Akt-signaling pathway, and importantly, the survival of the transplanted cells of rat origin (Table).
Conclusions: The addition of MSC to SMB cell-sheet enhanced the paracrine mechanics and, consequently, the functional recovery in the rat ICM model, suggesting a possible strategy in the clinical arena.
- © 2011 by American Heart Association, Inc.