Physiological Microenvironmental Conditions in Different Scalable Culture Systems for Pluripotent Stem Cell Expansion and Differentiation

Fuad G. Torizal1, *, Ikki Horiguchi2, Yasuyuki Sakai2, 3
1 Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan
2 Department of Chemical Systems Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan
3 International Research Center on Integrative Biomedical Systems CIBiS, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan

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© 2019 Torizal et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, Japan; Tel: +81-3-5841-7032; Fax: +81-3-5841-7032; E-mail:


Human Pluripotent Stem Cells (PSCs) are a valuable cell type that has a wide range of biomedical applications because they can differentiate into many types of adult somatic cell. Numerous studies have examined the clinical applications of PSCs. However, several factors such as bioreactor design, mechanical stress, and the physiological environment have not been optimized. These factors can significantly alter the pluripotency and proliferation properties of the cells, which are important for the mass production of PSCs. Nutritional mass transfer and oxygen transfer must be effectively maintained to obtain a high yield. Various culture systems are currently available for optimum cell propagation by maintaining the physiological conditions necessary for cell cultivation. Each type of culture system using a different configuration with various advantages and disadvantages affecting the mechanical conditions in the bioreactor, such as shear stress. These factors make it difficult to preserve the cellular viability and pluripotency of PSCs. Additional limitations of the culture system for PSCs must also be identified and overcome to maintain the culture conditions and enable large-scale expansion and differentiation of PSCs. This review describes the different physiological conditions in the various culture systems and recent developments in culture technology for PSC expansion and differentiation.

Keywords: Pluripotent stem cells, Culture systems, Mechanical stress, Microenvironmental condition, Mass production, Bioreactor.