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Biomaterials. 2017 Jul;131:47-57. doi: 10.1016/j.biomaterials.2017.03.037. Epub 2017 Mar 28.

Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue.

Author information

1
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
2
Bio-Acoustic MEMS in Medicine (BAMM) Lab, Department of Radiology, Stanford University School of Medicine, Canary Center for Early Cancer Detection, Stanford, CA, USA; Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan, China; Institute of Model Animal of Wuhan University, Wuhan, China.
3
Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
4
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Biology Program, California State University Channel Islands, Camarillo, CA, USA.
5
The Nanoscience Centre, University of Cambridge, Cambridge, United Kingdom.
6
Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston 02144, MA, USA.
7
Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston 02144, MA, USA; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway 08854, NJ, USA.
8
Department of Orthopaedic Surgery, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
9
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
10
Bio-Acoustic MEMS in Medicine (BAMM) Lab, Department of Radiology, Stanford University School of Medicine, Canary Center for Early Cancer Detection, Stanford, CA, USA; Department of Electrical Engineering (by Courtesy), Stanford University School of Engineering, Stanford, CA, USA. Electronic address: utkan@stanford.edu.
11
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA. Electronic address: smwu@stanford.edu.

Abstract

The creation of physiologically-relevant human cardiac tissue with defined cell structure and function is essential for a wide variety of therapeutic, diagnostic, and drug screening applications. Here we report a new scalable method using Faraday waves to enable rapid aggregation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into predefined 3D constructs. At packing densities that approximate native myocardium (108-109 cells/ml), these hiPSC-CM-derived 3D tissues demonstrate significantly improved cell viability, metabolic activity, and intercellular connection when compared to constructs with random cell distribution. Moreover, the patterned hiPSC-CMs within the constructs exhibit significantly greater levels of contractile stress, beat frequency, and contraction-relaxation rates, suggesting their improved maturation. Our results demonstrate a novel application of Faraday waves to create stem cell-derived 3D cardiac tissue that resembles the cellular architecture of a native heart tissue for diverse basic research and clinical applications.

KEYWORDS:

Cardiac regenerative medicine; Cardiomyocytes; Human induced pluripotent stem cells; Sound wave cellular patterning

[Indexed for MEDLINE]
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