Simulated Microgravity and 3D Culture Enhance Induction, Viability, Proliferation and Differentiation of Cardiac Progenitors from Human Pluripotent Stem Cells

• Type of Material: Article
• Authors: Rajneesh Jha, Emory University; Qingling Wu, Emory University; Monalisa Singh, Emory University; Marcela K. Preininger, Emory University; Pengcheng Han, Emory University; Guoliang Ding, Emory University; Hee Cho, Emory University; Hanjoong Jo, Emory University; Kevin Maher, Emory University; Mary Wagner, Emory University; Chunhui Xu, Emory University
• Language: English
• Date: 2016-08-05
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2016, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep30956
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 6
• Start Page: 30956
• End Page: 30956
• Grant/Funding Information: This study was supported in part by grants GA-2014-126 from the Center for the Advancement of Science in Space (CASIS) and R21HL118454 from the NIH. Q.W. and M.P.K. were supported by the Center for Pediatric Nanomedicine at Emory/Georgia Tech.
• Keywords: Stem-cell differentiation; CARDIOVASCULAR PROGENITORS; Cell growth; Cardiology; CARDIOMYOCYTES; FUNCTIONAL MATURATION; RANDOM POSITIONING MACHINE; GROWING TISSUES; REPAIR; Multidisciplinary Sciences; Science & Technology; GENERATION
• Research Categories: Engineering, Biomedical; Health Sciences, General

Abstract

Efficient generation of cardiomyocytes from human pluripotent stem cells is critical for their regenerative applications. Microgravity and 3D culture can profoundly modulate cell proliferation and survival. Here, we engineered microscale progenitor cardiac spheres from human pluripotent stem cells and exposed the spheres to simulated microgravity using a random positioning machine for 3 days during their differentiation to cardiomyocytes. This process resulted in the production of highly enriched cardiomyocytes (99% purity) with high viability (90%) and expected functional properties, with a 1.5 to 4-fold higher yield of cardiomyocytes from each undifferentiated stem cell as compared with 3D-standard gravity culture. Increased induction, proliferation and viability of cardiac progenitors as well as up-regulation of genes associated with proliferation and survival at the early stage of differentiation were observed in the 3D culture under simulated microgravity. Therefore, a combination of 3D culture and simulated microgravity can be used to efficiently generate highly enriched cardiomyocytes.