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Bioengineering 2017, 4(2), 47; doi:10.3390/bioengineering4020047

Hypoxic Three-Dimensional Scaffold-Free Aggregate Cultivation of Mesenchymal Stem Cells in a Stirred Tank Reactor

1
Department of Biotechnology, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria
2
Translational Center, University Hospital Wuerzburg, Roentgenring 11, 97070 Wuerzburg, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Christoph Herwig
Received: 26 April 2017 / Revised: 19 May 2017 / Accepted: 21 May 2017 / Published: 23 May 2017
(This article belongs to the Special Issue Hybrid Modelling and Multi-Parametric Control of Bioprocesses)
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Abstract

Extensive expansion of mesenchymal stem cells (MSCs) for cell-based therapies remains challenging since long-term cultivation and excessive passaging in two-dimensional conditions result in a loss of essential stem cell properties. Indeed, low survival rate of cells, alteration of surface marker profiles, and reduced differentiation capacity are observed after in vitro expansion and reduce therapeutic success in clinical studies. Remarkably, cultivation of MSCs in three-dimensional aggregates preserve stem cell properties. Hence, the large scale formation and cultivation of MSC aggregates is highly desirable. Besides other effects, MSCs cultivated under hypoxic conditions are known to display increased proliferation and genetic stability. Therefore, in this study we demonstrate cultivation of adipose derived human MSC aggregates in a stirred tank reactor under hypoxic conditions. Although aggregates were exposed to comparatively high average shear stress of 0.2 Pa as estimated by computational fluid dynamics, MSCs displayed a viability of 78–86% and maintained their surface marker profile and differentiation potential after cultivation. We postulate that cultivation of 3D MSC aggregates in stirred tank reactors is valuable for large-scale production of MSCs or their secreted compounds after further optimization of cultivation parameters. View Full-Text
Keywords: mesenchymal stem cells; scaffold-free; aggregate cultivation; stirred tank reactor; dynamic cultivation; hypoxia; stemness; computational fluid dynamics mesenchymal stem cells; scaffold-free; aggregate cultivation; stirred tank reactor; dynamic cultivation; hypoxia; stemness; computational fluid dynamics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Egger, D.; Schwedhelm, I.; Hansmann, J.; Kasper, C. Hypoxic Three-Dimensional Scaffold-Free Aggregate Cultivation of Mesenchymal Stem Cells in a Stirred Tank Reactor. Bioengineering 2017, 4, 47.

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