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

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External Research Organisations

  • University of Natural Resources and Applied Life Sciences (BOKU)
  • Julius Maximilian University of Würzburg
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Details

Original languageEnglish
Article number47
Number of pages12
JournalBioengineering
Volume4
Issue number2
Publication statusPublished - 23 May 2017
Externally publishedYes

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.

Keywords

    Aggregate cultivation, Computational fluid dynamics, Dynamic cultivation, Hypoxia, Mesenchymal stem cells, Scaffold-free, Stemness, Stirred tank reactor

ASJC Scopus subject areas

Cite this

Hypoxic Three-Dimensional Scaffold-Free Aggregate Cultivation of Mesenchymal Stem Cells in a Stirred Tank Reactor. / Egger, Dominik; Schwedhelm, Ivo; Hansmann, Jan et al.
In: Bioengineering, Vol. 4, No. 2, 47, 23.05.2017.

Research output: Contribution to journalArticleResearchpeer review

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 May 23;4(2):47. doi: 10.3390/bioengineering4020047
Egger, Dominik ; Schwedhelm, Ivo ; Hansmann, Jan et al. / Hypoxic Three-Dimensional Scaffold-Free Aggregate Cultivation of Mesenchymal Stem Cells in a Stirred Tank Reactor. In: Bioengineering. 2017 ; Vol. 4, No. 2.
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AU - Egger, Dominik

AU - Schwedhelm, Ivo

AU - Hansmann, Jan

AU - Kasper, Cornelia

PY - 2017/5/23

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AB - 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.

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KW - Computational fluid dynamics

KW - Dynamic cultivation

KW - Hypoxia

KW - Mesenchymal stem cells

KW - Scaffold-free

KW - Stemness

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