Abstract 14660: Xeno-Free Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Cell Sheet Transplantation Promise the Safety and Effectiveness in the Treatment for Heart Failure
Background: Human Induced pluripotent stem cells (hiPSC) have a potential to propose new era for the treatment for cardiovascular disease, while the safety in hiPSC have great concern for clinical application containing xeno-biomaterials for differentiation in cardiomyocytes (CMs). We have explored synthetic small molecules, KY, instead of standard xeno-materials such as BMP4, Activin A or insulin, to induce cardiomyogenic differentiation. We herein hypothesized that xeno-free culture condition can induce adequate cardiogenic differentiation in hiPSC, that have therapeutic effectiveness on chronic myocardial infarction (MI) in rat.
Methods: KY was added to hiPSCs, which showed 91.2±4%-positivity in cardiac-troponin T (cTnT). Scaffold-free cardiac graft was produced by hiPSC-CMs that were cultured in thermoresponsive dishes, and transplanted over the cardiac surface of athymic nude rats that were subjected to left coronary artery ligation 2 weeks prior to the treatment or sham operated.
Results: Echocardiographically, ejection fraction significantly recovered after the treatment in the hiPSC-CM group (43.8±6.7% at baseline, 68.9±9.2% at 1 week, 70.8±6.8% at 2 weeks, and 75.5±10% at 4 weeks), whereas the sham group showed gradual reduction (43.5±4.8% at baseline, 40.5±4.6% at 1 week, 37.9±6.7% at 2 weeks, and 32.3±5.5% at 4 weeks). Immunohistochemistry showed that a large number of cTnT and human nuclear antigen double positive-hiPSC-CMs were present in the lateral cardiac surface in the hiPSC-CM transplanted hearts. The number of CD31-positve capillary in the infarct-border area was greater in the hiPSC-CM group (P<0.01) than the sham group. Real-time PCR analysis revealed that expressions of HGF, VEGF, SDF-1, VE-cadherin, CD31 and Angiopoietin-1 were significantly increased in the the hiPSC-CM group (P<0.01) at 3 days after transplantation compared with the sham group, but, at 4 weeks after transplantation, expressions of HGF and CD31 were significantly increased (P<0.05).
Conclusion: Xeno-free culture condition can induce adequate cardiogenic differentiation in hiPSC that have potential in functional effectiveness on rat chronic MI heart, promising safe clinical application in hiPSC.
Author Disclosures: M. Shiozaki: None. S. Miyagawa: None. S. Fukushima: None. I. Minami: None. S. Yajima: None. K. Domae: None. A. Saito: None. T. Asada: None. N. Nakatsuji: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.