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Author Notes:

Correspondence and requests for materials should be addressed to C.X. (email: chunhui.xu@emory.edu).

R.J. and C.X. designed the study and wrote the manuscript.

R.J., Q.W. and M.S. performed and analyzed cellular and molecular experiments.

M.K.P. and M.B.W. performed and analyzed calcium transient recordings.

G.D., P.H. and H.C.C. performed and analyzed patch-clamp electrophysiology.

H.J. contributed equipment and analysis tools for simulated microgravity.

K.O.M., M.B.W. and C.X. conceived the study.

For acknowledgements, please see the full article.

The authors declare no competing financial interests.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Multidisciplinary Sciences
  • RANDOM POSITIONING MACHINE
  • CARDIOVASCULAR PROGENITORS
  • FUNCTIONAL MATURATION
  • GROWING TISSUES
  • CARDIOMYOCYTES
  • GENERATION
  • REPAIR
  • Cell growth
  • Stem-cell differentiation
  • Cardiology

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

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Journal Title:

Scientific Reports

Volume:

Volume 6

Publisher:

, Pages 30956-30956

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2016, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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