Abstract 16426: Vasculature-Designed 3-Dimensional Artificial Cardiac Tissue Derived From Human Induced Pluripotent Stem Cells: An Engineered Cardiac Graft to Enhance Vascular Network Formation With the Scarred Myocardium in Rat
Introduction: While transplantation of artificial cardiac tissue is a promising strategy to treat advanced chronic myocardial infarction (MI) heart, ischemia in the graft is a concern as a limiting factor of its therapeutic potential. We recently developed a new technology by which human induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs) formed 3-dimensional (D) artificial cardiac tissue including microvascular network in vitro. We hypothesized that transplanted artificial cardiac tissue may be integrated into the MI heart, leading to functional recovery.
Methods: hiPSC-CMs, endothelial cells and cardiac fibroblasts of human origin were coated with fibronectin and gelatin, and then incubated in cell culture insert to reconstruct vascularized 3D cardiac tissue in vitro, which was epicardially transplanted into the scarred myocardium of nude rat that was subjected to left coronary artery ligation X weeks prior to the treatment, or sham operation was performed (n=10 each).
Results: The 3D-cardiac tissue transplant yielded a significant increase in echocardiographical ejection fraction over the 4 weeks (43.2±3.6% vs 51.6±5.5 %, P <0.05), whereas the control group exhibited a significant decrease (47.2±5.1% vs 40.9±3.2%, P <0.05). Histologically, a rich graft was present in the scarred myocardium at 4 weeks (A). While most of the cellular components in the graft was human cardiac troponin T-positive cardiac myocytes, they were surrounded by human CD31-positive luminal structures (B and C). In addition, a greater number microvascular structure including rat smooth muscle actin-positive cells were present in the scarred area of the transplanted group compared to those in the sham group .
Conclusions: A vascularized artificial cardiac tissue was well integrated into the scarred myocardium with mature microvascular connection, warranting a cardiac tissue supplementing therapy by iPSC-CM-derived artificial cardiac tissue transplantation.
- Regenerative medicine stem cells
- Cellular Engineering
- Cellular Therapy
- Heart failure
- Ischemic heart disease
Author Disclosures: J. Yokoyama: None. S. Miyagawa: None. S. Fukushima: None. Y. Takamura: None. Y. Shima: None. M. Akashi: None. K. Toda: None. T. Ueno: None. T. Kuratani: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.