title: Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes.
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 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.
authors.affiliation: Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Campus Grüental, 8820 Wädenswil, Switzerland.
authors.forename: Valentin
authors.initials: V
authors.lastname: Jossen
authors.affiliation: Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Campus Grüental, 8820 Wädenswil, Switzerland.
authors.forename: Cedric
authors.initials: C
authors.lastname: Schirmer
authors.affiliation: Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Campus Grüental, 8820 Wädenswil, Switzerland.
authors.forename: Dolman
authors.initials: D
authors.lastname: Mostafa Sindi
authors.affiliation: Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Campus Grüental, 8820 Wädenswil, Switzerland.
authors.forename: Regine
authors.initials: R
authors.lastname: Eibl
authors.affiliation: Department of Process Engineering, Chair of Chemical and Process Engineering, Technical University of Berlin, Strasse des 17.Juni 135, 10623 Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kraume
authors.affiliation: Department of Bioprocess and Biosystems Engineering, Technical University of Hamburg, Denickestrasse 1, 21073 Hamburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Pörtner
authors.affiliation: Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Campus Grüental, 8820 Wädenswil, Switzerland.
authors.forename: Dieter
authors.initials: D
authors.lastname: Eibl