Microscale Generation of Cardiospheres Promotes Robust Enrichment of Cardiomyocytes Derived from Human Pluripotent Stem Cells

• Type of Material: Article
• Authors: Doan C. Nguyen, Emory University; Tracy A. Hookway, Georgia Institute of Technology and Emory University; Qingling Wu, Emory University; Rajneesh Jha, Emory University; Marcela K. Preininger, Emory University; Xuemin Chen, Emory University; Charles Easley, Emory University; Paul Spearman, Emory University; Shriprasad Deshpande, Emory University; Kevin Maher, Emory University; Mary Wagner, Emory University; Todd McDevitt, Emory University; Chunhui Xu, Emory University
• Language: English
• Date: 2014-08-12
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2014 The Authors
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.stemcr.2014.06.002
• Title of Journal or Parent Work: Stem Cell Reports
• ISSN: 2213-6711
• Volume: 3
• Issue: 2
• Start Page: 260
• End Page: 268
• Grant/Funding Information: This work was supported in part by the Emory Children’s Center (C.X.); the Clinical and Translational Sciences Award Program of the National Center for Advancing Translational Sciences, NIH (PHS grant ULITR00454 to C.X. and T.C.M.); the National Science Foundation (CBET 0939511 to T.C.M.); CASIS (GA-2014-126 to C.X.), and the NIH (R21HL118454 to C.X.). Q.W. and M.K.P. were supported by the Center for Pediatric Nanomedicine under the direction of Dr. Gang Bao.
• Keywords: Science & Technology; Life Sciences & Biomedicine; MICROTISSUES; FUNCTIONAL MATURATION; Cell Biology; Cell & Tissue Engineering; DIFFERENTIATION; CULTURE
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, General; Biology, Cell

Abstract

Cardiomyocytes derived from human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, disease modeling, and drug discovery, all of which require enriched cardiomyocytes, ideally ones with mature phenotypes. However, current methods are typically performed in 2D environments that produce immature cardiomyocytes within heterogeneous populations. Here, we generated 3D aggregates of cardiomyocytes (cardiospheres) from 2D differentiation cultures of hPSCs using microscale technology and rotary orbital suspension culture. Nearly 100% of the cardiospheres showed spontaneous contractility and synchronous intracellular calcium transients. Strikingly, from starting heterogeneous populations containing ∼10%-40% cardiomyocytes, the cell population within the generated cardiospheres featured ∼80%-100% cardiomyocytes, corresponding to an enrichment factor of up to 7-fold. Furthermore, cardiomyocytes from cardiospheres exhibited enhanced structural maturation in comparison with those from a parallel 2D culture. Thus, generation of cardiospheres represents a simple and robust method for enrichment of cardiomyocytes in microtissues that have the potential use in regenerative medicine as well as other applications. © 2014 The Authors.