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Title: Theoretical and practical issues that are relevant when scaling up hMSC microcarrier production processes
Authors : Jossen, Valentin
Schirmer, Cedric
Mostafa Sindi, Dolman
Eibl-Schindler, Regine
Kraume, Matthias
Pörtner, Ralf
Eibl, Dieter
Published in : Stem Cells International
Volume(Issue) : 2016
Issue : 4760414
Publisher / Ed. Institution : Hindawi
Publisher / Ed. Institution: New York
Issue Date: 2016
License (according to publishing contract) : CC BY 4.0: Namensnennung 4.0 International
Type of review: Peer review (Publication)
Language : English
Subject (DDC) : 660.6: Biotechnology
Abstract: The potential of human mesenchymal stem cells (hMSCs) for allogeneic cell therapies has created a large amount of interest. However, this presupposes the availability of efficient scale-up procedures. Promising results have been reported for stirred bioreactors that operate with microcarriers. Recent publications focusing on microcarrier-based stirred bioreactors have demonstrated the successful use of Computational FluidDynamics (CFD) and suspension criteria (NS1u,NS1) for rapidly scaling up hMSC expansions from mL- to pilot scale. Nevertheless, one obstacle may be the formation of large microcarrier-cell-aggregates, which may result in mass transfer limitations and inhomogeneous distributions of stem cells in the culture broth.The dependence of microcarrier-cell-aggregate formation on impeller speed and shear stress levels was investigated for human adipose derived stromal/stem cells (hASCs) at the spinner scale by recording the Sauter mean diameter (d 32) versus time. Cultivation at the suspension criteria provided d 32 values between 0.2 and 0.7 mm, the highest cell densities (1.25 × 106 cells mL−1 hASCs), and the highest expansion factors (117.0 ± 4.7 on day 7), while maintaining the expression of specific surface markers. Furthermore, suitability of the suspension criterion NS1u was investigated for scaling up microcarrier-based processes in wave-mixed bioreactors for the first time.
Departement: Life Sciences und Facility Management
Publication type: Article in scientific Journal
DOI : 10.1155/2016/4760414
ISSN: 1687-9678
Appears in Collections:Publikationen Life Sciences und Facility Management

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