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Generation of cardiac spheres from primate pluripotent stem cells in a small molecule-based 3D system

Paper ID Volume ID Publish Year Pages File Format Full-Text
5585 405 2015 12 PDF Available
Title
Generation of cardiac spheres from primate pluripotent stem cells in a small molecule-based 3D system
Abstract

Pluripotent stem cell (PSC) usage in heart regenerative medicine requires producing enriched cardiomyocytes (CMs) with mature phenotypes in a defined medium. However, current methods are typically performed in 2D environments that produce immature CMs. Here we report a simple, growth factor-free 3D culture system to rapidly and efficiently generate 85.07  ±  1.8% of spontaneously contractile cardiac spheres (scCDSs) using 3D-cultured human and monkey PSC-spheres. Along with small molecule-based 3D induction, this protocol produces CDSs of up to 95.7% CMs at a yield of up to 237 CMs for every input pluripotent cell, is effective for human and monkey PSCs, and maintains 81.03  ±  12.43% of CDSs in spontaneous contractibility for over three months. These CDSs displayed CM ultrastructure, calcium transient, appropriate pharmacological responses and CM gene expression profiles specific for maturity. Furthermore, 3D-derived CMs displayed more mature phenotypes than those from a parallel 2D-culture. The system is compatible to large-scaly produce CMs for disease study, cell therapy and pharmaceutics screening.

Keywords
Primate embryonic stem cells; 3D suspension culture of plurioptent stem cells; Small molecule-based 3D differentiation; Cardiac spheres; Cardiac maturity
First Page Preview
Generation of cardiac spheres from primate pluripotent stem cells in a small molecule-based 3D system
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 65, October 2015, Pages 103–114
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering