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Int J Biol Sci 2018; 14(5):485-496. doi:10.7150/ijbs.24681

Research Paper

The Suppression of Medium Acidosis Improves the Maintenance and Differentiation of Human Pluripotent Stem Cells at High Density in Defined Cell Culture Medium

Weiwei Liu1, Zhili Ren1, Kai Lu1, Chengcheng Song1, Edwin Chong Wing Cheung1, Zhou Zhou2, Guokai Chen1✉

1. University of Macau, Faculty of Health Sciences, Taipa, Macau
2. State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China

Abstract

Cell density has profound impacts on the cell culture practices of human pluripotent stem cells. The regulation of cell growth, cell death, pluripotency and differentiation converge at high density, but it is largely unknown how different regulatory mechanisms act at this stage. We use a chemically defined medium to systemically examine cellular activities and the impact of medium components in high-density culture. We show that medium acidosis is the main factor that alters cell cycle, gene expression and cellular metabolism at high cell density. The low medium pH leads to inhibition of glucose consumption, cell cycle arrest, and subsequent cell death. At high cell density, the suppression of medium acidosis with sodium bicarbonate (NaHCO3) significantly increases culture capacity for stem cell survival, derivation, maintenance and differentiation. Our study provides a simple and effective tool to improve stem cell maintenance and applications.

Keywords: Human pluripotent stem cells, acidosis, glycolysis, cell death, differentiation

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Liu W, Ren Z, Lu K, Song C, Cheung ECW, Zhou Z, Chen G. The Suppression of Medium Acidosis Improves the Maintenance and Differentiation of Human Pluripotent Stem Cells at High Density in Defined Cell Culture Medium. Int J Biol Sci 2018; 14(5):485-496. doi:10.7150/ijbs.24681. Available from http://www.ijbs.com/v14p0485.htm