Abstract 13166: Novel Heart Tissue Slice Enables Long-term Survival and Engraftment Following Transplantation in Ischemic Hearts
Introduction: New therapeutic cell delivery strategies are currently being tested to restore contractile function following myocardial infarction (MI). Cells are typically delivered via intramyocardial or intravascular routes. However, the engraftment of most cells is <1% after 4 weeks. We hypothesize that heart tissue slice (HTS) transplantation might lead to better cell survival and serve as a reference to assess efficacy and improve survival of engineered tissue constructs.
Methods & Results: Transgenic mouse hearts (GFP+, luc+) were cut into slices of defined thickness before transplantation onto normal or infarcted hearts (nod/scid mice; n=40). Animals underwent repeated bioluminescence imaging and immunofluorescence validation of graft size and composition. Following transplantation, HTS lost viable cells for the first 7 days with no further loss seen afterwards (p=0.34 day 7 vs. 56) preserving 33±4% at 2 month (300μm thickn.). HTS viability at 4 weeks depended on initial slice thickness (100μm 17±5%, 200μm 22±4%, 400μm 13±4%, 800μm 8±3%) indicating diffusion limited survival. The total number of cells alive at 4 weeks was higher for HTS with 200 and 400 μm thickness compared to 100 and 800 μm (p<0.05). We found good survival of HTS transplanted onto infarcted hearts (100μm 8±3%, 200μm 16±6%, 400μm 12±5%, 800μm 2±1%), but lower overall survival compared to control (p<0.05). Immunofluorescence 4 weeks post-surgery confirmed presence of robustly viable adult tissues within HTS recipients (Fig. 1).
Conclusion: We demonstrate for the first time that transplantation of heart tissue slices can promote significant cell survival and preserves tissue morphology, compared to drastic cell death following direct cell injections. Studies are ongoing to quantify the extent of functional improvement following HTS transplantation in a rodent MI model.
Fig. 1: Image of grafted HTS 4 weeks post-surgery and whole heart fluorescence image .
- © 2013 by American Heart Association, Inc.