Abstract 11866: Development of Vascular-Rich Tissue Containing Cardiomyocytes Derived from Human iPS Cells in vivo
Introduction Transplantation of cardiomyocytes derived from induced pluripotent stem cells (iPS-CM) is promising to generate new functional myocardium in situ, while survival and functionality of the transplanted cells are critical for considering this therapeutic impact. The cell sheet method has been used to transplant many functional cells; however, the potential ischemia might limit the cell survival. The omentum, which is known to have rich vasculature and angiogenic factors, is expected to be a blood supply source. We hypothesized that transplantation of iPS-CM cell sheets combined with omentum flap may deliver a large number of functional iPS-CMs via enhanced blood supply
Methods and Results Retrovirally established human iPS cells were treated with Wnt signaling molecules to induce cardiomyogenic differentiation, followed by superparamagnetic iron oxide (SPIO) labeling. Cell sheets were created from the magnetically labeled iPS-CMs using thermoresponsive dishes and transplanted to porcine hearts with or without the omentum flap (n=8 each). Two months after transplantation, survival of the SPIO-labeled iPS-CMs, assessed by MRI, was significantly greater in the pigs with the omentum than in those without the omentum (90±7% vs 64±9%, P<0.01, Figure); histologically, vascular density in the transplanted area, assessed by immunohistochemical analysis for vWF, was significantly greater in the pigs with the omentum (225±74 units/mm2) than in those without the omentum (55±7 units/mm2, P<0.01). The transplanted tissues contained abundant myosin heavy chain positive cells surrounded by vascular rich structure (Figure).
Conclusion The omentum flap enhanced the survival of iPS-CMs after transplantation via increased angiogenesis, suggesting the rationale of this strategy in a clinical scenario. The combination of iPS-CMs and the omentum flap may be promising technique for the development of tissue-engineered vascular rich new myocardium in vivo.
- © 2012 by American Heart Association, Inc.