title: Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue.
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 (108-109cells/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.
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Vahid
authors.initials: V
authors.lastname: Serpooshan
authors.affiliation: 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.
authors.forename: Pu
authors.initials: P
authors.lastname: Chen
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Haodi
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
authors.forename: Soah
authors.initials: S
authors.lastname: Lee
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hu
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Biology Program, California State University Channel Islands, Camarillo, CA, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Venkatraman
authors.affiliation: The Nanoscience Centre, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Adarsh Venkataraman
authors.initials: AV
authors.lastname: Ganesan
authors.affiliation: Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston 02144, MA, USA.
authors.forename: Osman Berk
authors.initials: OB
authors.lastname: Usta
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Yarmush
authors.affiliation: Department of Orthopaedic Surgery, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Utkan
authors.initials: U
authors.lastname: Demirci
authors.affiliation: 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.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wu
mesh_terms: D000162:Acoustics; D062028:Bioprinting / Q000295:instrumentation / Q000379:methods*; D002478:Cells, Cultured; D004867:Equipment Design; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D013016:Sound; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
keywords: Cardiac regenerative medicine; Cardiomyocytes; Human induced pluripotent stem cells; Sound wave cellular patterning