Abstract 18056: Novel Stem Cell Therapy for Heart Failure Using 3D Printed Cardiac Tissue
Introduction: Alternative treatments for heart failure such as stem cell therapy and tissue engineering approaches have been developed recently. However attempts to demonstrate significant myocardial regeneration with conventional cell delivery platforms have been limited. We have developed a novel method to deliver stem cells using Bio 3D printed cardiac patches free of biomaterial and have characterized the electrophysiological and histological properties of these patches.
Methods: Human induced pluripotent stem cell-derived cardiomyocytes (CM), fibroblasts (FB) and endothelial cells (EC) were aggregated to create mixed cell spheroids comprised of a range of total numbers of cells and various CM:FB:EC cell ratios. Cardiac patches were created from mixed cell spheroids at various cell ratios (CM:FB:EC = 70:15:15, 60:25:15, 45:45:10) using a Bio 3D printer system. Cardiac patches were analyzed with static and video microscopy, immunohistochemical staining (TUNEL, Caspase-3, Troponin, CD31, Vimentin) with confocal microscopy and optical mapping after staining with a voltage sensitive dye.
Results: Spheroids increased in diameter with increasing cell numbers. There was no spheroid formation in the absence of FB. Cardiac patches of all cell ratios beat spontaneously 6 days after 3D-printing at 31 ± 3 bpm. Cardiac patches (70:15:15, 60:25:15) exhibited ventricular-like action potential waveforms and continuous albeit slow conduction (CV = 2.7 cm/s). Immunohistochemistry revealed reorganization of CM, FB and ECs with sufficient cell viability.
Conclusions: The biomaterial-free 3D-printed cardiac tissue created from hiPSCs exhibited spontaneous beating, electrical integration of component cardiospheres and ventricular myocyte-like cellular electrophysiological properties. This constitutes a significant step towards a new generation of stem cell treatment for heart failure.
Author Disclosures: C. Ong: None. T. Fukunishi: None. A. Blazeski: None. H. Zhang: None. A.R. Nashed: None. L. Vricella: None. J. Conte: None. L. Tung: None. G.F. Tomaselli: None. N. Hibino: None.
- © 2016 by American Heart Association, Inc.