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Publisher DOI: 10.1155/2016/4760414
Title: Theoretical and practical issues that are relevant when scaling up hMSC microcarrier production porocesses
Language: English
Authors: Jossen, Valentin 
Schirmer, Cedric 
Mostafa Sindi, Dolman 
Eibl, Regine 
Kraume, Matthias 
Pörtner, Ralf  
Eibl, Dieter 
Issue Date: 2016
Publisher: Sage-Hindawi
Source: Stem cells international (2016): 4760414-15 (2016)
Journal or Series Name: Stem cells international 
Abstract (english): 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 Fluid Dynamics (CFD) and suspension criteria (N S1u , N S1) 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 × 10(6) 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 N S1u was investigated for scaling up microcarrier-based processes in wave-mixed bioreactors for the first time.
DOI: 10.15480/882.2127
ISSN: 1687-9678
Institute: Bioprozess- und Biosystemtechnik V-1 
Type: (wissenschaftlicher) Artikel
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