Introduction:
iPS cell-derived cardiac cell sheet (iPS sheet) transplantation is expected to have both cytokine paracrine effect and mechanical effect on the failed heart. In order to clarify the latter effect, we utilized the cardiac simulator “UT-Heart” to quantitatively evaluate the improvement of pumping function of the left ventricle with myocardial infarction covered by the thickened iPS sheet in silico. The direct mechanical impact of iPS sheet with various thicknesses was calculated first, and then the remodeling effect of fiber orientation was investigated.
Patient and Method:
An infarcted heart model based on the actual patient’s data was created on the computer and an iPS sheet was virtually implanted under the following assumptions: (1) electrophysiologically synchronized with the underlying cardiac muscle, (2) covered the infarct area entirely, (3) the fiber orientation of sheet was parallel to that of the epicardial tissue when attached, (4) if remodeling occurs, the fiber orientations of myocardial tissue and the attached sheet change such that the contraction force and the fiber strains are homogenized in the heart. The UT-Heart simulation was performed while changing iPS sheet thickness from 1mm to 5mm.
Results:
The LVEF of 18.0 % at pre-implantation was improved to 18.5 % with 1 mm thickness, and 19.6 % with 5 mm thickness without remodeling assumption as shown in the left of the figure. If LV remodeling occurs, the LVEF was improved to 20.9 % with 1mm thickness and 22.8 % with 5mm thickness. The LVESP was 10 mmHg higher than that of pre-implantation even when 1mm thickness was implanted.
Conclusion:
The direct mechanical effect of the thickened iPS sheet on the distressed LV was quantitatively evaluated in silico. Because changes in fiber orientation have a significant impact on pumping function, the remodeling assumption used herein should be experimentally verified in the future.