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Author Notes:

Corresponding author Email: chunhui.xu@emory.edu

C.X. and T.C.M. jointly conceived the study; D.C.N., T.A.H., Q.W., R.J., and M.K.P. performed research; X.C., C.A.E., P.S., S.R.D., K.M., and M.B.W. contributed new reagents and analytic tools; D.C.N., T.A.H., Q.W., R.J., M.K.P., and M.B.W. analyzed data; D.C.N. and C.X. wrote the paper; and T.A.H., M.B.W., and T.C.M. edited the paper.

We thank the staff of the Emory Children’s Pediatric Research Flow Cytometry Core for training on flow cytometry.

Subjects:

Research Funding:

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
  • Cell & Tissue Engineering
  • Cell Biology
  • FUNCTIONAL MATURATION
  • DIFFERENTIATION
  • MICROTISSUES
  • CULTURE

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

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Journal Title:

Stem Cell Reports

Volume:

Volume 3, Number 2

Publisher:

, Pages 260-268

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2014 The Authors

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits distribution, public display, and publicly performance, making multiple copies, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author. This license prohibits exercising rights for commercial purposes.

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