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J Biotechnol. 2019 Oct 10;304:16-27. doi: 10.1016/j.jbiotec.2019.08.002. Epub 2019 Aug 5.

Using computational fluid dynamics (CFD) modeling to understand murine embryonic stem cell aggregate size and pluripotency distributions in stirred suspension bioreactors.

Author information

1
Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada; Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada.
2
Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada; Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada.
3
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada.
4
Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada.
5
Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada; Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada; Department of Chemical and Petroleum Engineering, Schulich School of Engineering, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N 1N4, Canada. Electronic address: mskallos@ucalgary.ca.

Abstract

Computational fluid dynamics (CFD) modeling can be applied to understand hydrodynamics in stirred suspension bioreactors, which can in turn affect cell viability, proliferation, pluripotency and differentiation. In this study, we developed a CFD model to determine the effects of average shear rates and turbulent eddies on the formation and growth of murine embryonic stem cell aggregates. We found a correlation between average eddy size and aggregate size, which depended on bioreactor agitation rates. By relating these computational and biological variables, CFD modeling can predict optimal agitation rates to grow embryonic stem cell aggregates in stirred suspension bioreactors. To examine the effect of hydrodynamics on pluripotency, mESCs cultured in bioreactors under various agitation rates were tested for SSEA-1, Sox-2, and Nanog expression. Cells maintained a minimum of 95% positive expression with no change in the intensity distribution pattern between the different bioreactor conditions. This indicates that the average level of pluripotency marker expression is independent of changes in the hydrodynamic profile and resulting aggregate size distribution. The findings here can be further extended to other cell types that grow as aggregates in stirred suspension bioreactors and offer important insights necessary to realize cell therapies.

KEYWORDS:

Computational fluid dynamic modeling; Embryonic stem cells; Stirred suspension bioreactors

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