Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses

• DOI: 10.1038/srep24726
• Publication Date: 2016-04-20T09:26:48Z
• Authors: Nathaniel Huebsch; Peter Loskill; Nikhil Deveshwar; C. Ian Spencer; Luke M. Judge; Mohammad A. Mandegar; Cade B. Fox; Tamer M.A. Mohamed; Zhen Ma; Anurag Mathur; Alice M. Sheehan; Annie Truong; Mike Saxton; Jennie Yoo; Deepak Srivastava; Tejal A. Desai; Po-Lin So; Kevin E. Healy; Bruce R. Conklin
• Keywords: Contractility; Cardiac muscle

Abstract Tissue engineering approaches have the potential to increase physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex not amenable mass production, limiting ability use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do facilitate assembly elongated muscle or direct force measurements. Here we describe an approach that combines features cardiospheres: Micro-Heart (μHM) arrays, in which fibers formed fabricated template, with few 2,000 iPS-CM individual Within μHM, exhibit uniaxial contractility alignment, robust sarcomere reduced variability hypersensitivity responsiveness, compared monolayers same cellular composition. μHM mounted onto standard measurement apparatus exhibited a Frank-Starling response external stretch dose-dependent inotropic β-adrenergic agonist isoproterenol. Based on ease fabrication, production small number required form this system provides potentially powerful tool study cardiomyocyte maturation, cardiotoxicology vitro .