Abstract 17985: Transplanted Induced Pluripotent Stem Cells-derived Cardiomyocytes Functionally and Structurally Integrates into the Infract Heart to Induce Reverse LV Remodeling in Experimental Animal Models
Background: Somatic stem cell therapy has been shown to produce modest positive impacts on cardiac performance of hearts with chronic myocardial infarction (MI) by paracrine effects, but not by differentiation into functional cardiomyocytes. In contrast, induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) are expected to have a potential to work as functional cardiomyocytes in MI heart. We hypothesized that iPSC-CMs might functionally and electrically integrate into the infarct myocardium, leading to functional recovery compared with somatic stem cells.
Methods and Results: Immunosuppressed pigs underwent Ameroid-Ring placement to induce MI at one month prior to epicardial placement of scaffold-free cell-sheets of the following origins: human iPSC-CM (n=5), human mesenchymal stromal cell (MSC, n=4) or human skeletal myoblast (SkMB, n=6), or sham operation (n=6). All cell-treatment groups displayed a significantly greater ejection fraction at 8 weeks after treatment relative to before treatment; (iPSC-CM, +7.9±1.5%; MSC, +5.0±1.0%; SkMB, +5.2±2.8%), whereas the MI group showed a significant decline in ejection fraction (-5.3±1.6%). These improvements were accompanied by declines in myocardial wall stress in the infarct area. The improvement in the LV transverse peak strain indicating regional systolic function of the infarct area was the greatest in the iPSC-CM group (+6.4±2.9%), whereas, the MSC and the SkMB group failed to show improvement. This finding was consistent to the result by a rat model of chronic MI, which showed synchronized contraction of the iPSC-CMs in the infarct scar with the native heart.
Conclusion: Cell sheet transplantation of iPSC-CMs induced functional recovery in a porcine chronic MI model with synchronous beatings of the transplanted cells with native heart in comparison with somatic stem cells. It is indicated that iPSC-CM transplantation therapy may be effective in treating end-stage advanced cardiac failure.
Author Disclosures: M. Ishida: None. S. Miyagawa: None. S. Fukushima: None. A. Saito: None. S. Masuda: None. K. Domae: None. E. Ito: None. M. Shirai: None. J.T. Pearson: None. N. Yagi: None. K. Matsuura: None. Y. Sawa: None.
- © 2014 by American Heart Association, Inc.