Abstract 11283: Efficiently Piled-Up Cardiac Tissue-Like Sheets With Pluripotent Stem Cell-Derived Cells Robustly Promotes Cell Engraftment and Ameliorates Cardiac Dysfunction After Myocardial Infarction
Purpose: Sufficient engraftment of transplanted cardiovascular cell populations is desirable for successful cardiac cell therapy. We recently reported that the transplantation (TX) of three-layered cardiac sheet bioengineered with mouse embryonic stem cell (ESC)-derived cardiac cell populations ameliorated cardiac dysfunction of infarcted rat heart, mainly through neovascularization rather than direct contribution of regenerated myocardium. This result indicates that additional technology is still needed to realize regeneration of neo-myocardium. Gelatin hydrogel is a biodegradable biomaterial which supplements oxygen and nutrients and improves cell survival. Here we attempted to extend this technology to our sheets to efficiently generate a stacked cardiac sheet.
Methods and Results: Five mouse ESC-derived cardiac sheets were stacked with gelatin hydrogel microspheres in vitro. The thickness of viable stacked sheets among the sheets were significantly greater compared to those without gelatin hydrogel (thickness; 725.4 ± 6.1 vs. 204.7 ± 9.5μm, n=5, p < 0.0001). A Live/Dead assay showed that more cells survived in cell sheets with gelatin hydrogel microspheres than those without it (average live cell area; 0.171 vs. 0.076 mm2, average dead cell area; 0.000567 vs. 0.0406 mm2). TX of the cardiac sheets incorporated with gelatin hydrogel to rat myocardial infarction model showed highly efficient engraftment of the cardiac cell populations compared to those without it (engrafted area 1 week after TX; 4.44 ± 0.78, n=7 vs. 1.06 ± 0.65 mm2, n=3, p < 0.05, engrafted area 4 weeks after TX; 3.10 ± 0.47, n=5 vs. 0.67 ± 0.15 mm2, n=3, p < 0.001). Systolic function was significantly improved (FAC 4 weeks after TX; 59.0 ± 5.6 vs. 34.7 ± 2.8%, n=3, p=0.0220) and non-contracting length was significantly attenuated (AL 4 weeks after TX; 0.4 ± 0.7 vs. 14.9 ± 5.1%, n=3, p < 0.01)on echocardiogram after TX. Currently, 15 sheets were able to be piled up as a viable tissue-like structure, which reached to 1mm thickness in vitro.
Conclusions: Viable tissue-like structure with multi-layered cell sheets can be efficiently generated with gelatin hydrogel incorporation. This technology would be a breakthrough broadly for regenerative cell therapy strategies.
- © 2013 by American Heart Association, Inc.