Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes. (11th February 2016)

• Record Type: Journal Article
• Authors: Jossen, Valentin; Schirmer, Cedric; Mostafa Sindi, Dolman; Eibl, Regine; Kraume, Matthias; Pörtner, Ralf; Eibl, Dieter
• Other Names: deans Robert Academic Editor.
• Is Part Of: Stem cells international. Volume 2016(2016)
• Publication Date: 2016-02-11
• Subjects: Stem Cells -- Periodicals; Stem Cells -- Therapeutic use -- Periodicals; Stem Cells -- Transplantation -- Periodicals; 616.0277405
• DOI: 10.1155/2016/4760414
• Languages: English
• ISSNs: 1687-966X

Abstract

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 S 1 u, N S 1 ) 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 providedd 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 criterionN S 1 u was investigated for scaling up microcarrier-based processes in wave-mixed bioreactors for the first time.