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Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes

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. Recen...

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Autores principales: Jossen, Valentin, Schirmer, Cedric, Mostafa Sindi, Dolman, Eibl, Regine, Kraume, Matthias, Pörtner, Ralf, Eibl, Dieter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766353/
https://www.ncbi.nlm.nih.gov/pubmed/26981131
http://dx.doi.org/10.1155/2016/4760414
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author Jossen, Valentin
Schirmer, Cedric
Mostafa Sindi, Dolman
Eibl, Regine
Kraume, Matthias
Pörtner, Ralf
Eibl, Dieter
author_facet Jossen, Valentin
Schirmer, Cedric
Mostafa Sindi, Dolman
Eibl, Regine
Kraume, Matthias
Pörtner, Ralf
Eibl, Dieter
author_sort Jossen, Valentin
collection PubMed
description 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.
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spelling pubmed-47663532016-03-15 Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes Jossen, Valentin Schirmer, Cedric Mostafa Sindi, Dolman Eibl, Regine Kraume, Matthias Pörtner, Ralf Eibl, Dieter Stem Cells Int Research Article 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. Hindawi Publishing Corporation 2016 2016-02-11 /pmc/articles/PMC4766353/ /pubmed/26981131 http://dx.doi.org/10.1155/2016/4760414 Text en Copyright © 2016 Valentin Jossen et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jossen, Valentin
Schirmer, Cedric
Mostafa Sindi, Dolman
Eibl, Regine
Kraume, Matthias
Pörtner, Ralf
Eibl, Dieter
Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes
title Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes
title_full Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes
title_fullStr Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes
title_full_unstemmed Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes
title_short Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes
title_sort theoretical and practical issues that are relevant when scaling up hmsc microcarrier production processes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766353/
https://www.ncbi.nlm.nih.gov/pubmed/26981131
http://dx.doi.org/10.1155/2016/4760414
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