Conflict of interests: All authors except B. Rieger were employed or contracted by Roche Diagnostics GmbH during their contributions to this work.
Modulation of mesenchymal stromal cell characteristics by microcarrier culture in bioreactors
Article first published online: 14 JUL 2014
© 2014 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 111, Issue 11, pages 2290–2302, November 2014
How to Cite
Hupfeld, J., Gorr, I. H., Schwald, C., Beaucamp, N., Wiechmann, K., Kuentzer, K., Huss, R., Rieger, B., Neubauer, M. and Wegmeyer, H. (2014), Modulation of mesenchymal stromal cell characteristics by microcarrier culture in bioreactors. Biotechnol. Bioeng., 111: 2290–2302. doi: 10.1002/bit.25281
J. Hupfeld and R. Huss's present address is Apceth GmbH & Co. KG, Max-Lebsche-Platz 30, Munich 81377, Germany.
- Issue published online: 23 SEP 2014
- Article first published online: 14 JUL 2014
- Accepted manuscript online: 29 MAY 2014 05:37PM EST
- Manuscript Accepted: 30 APR 2014
- Manuscript Revised: 29 APR 2014
- Manuscript Received: 16 JAN 2014
- Bavarian Ministry of Economic Affairs, Infrastructure, Transport and Technology in Germany. Grant Number: 0703 68664/19/10/1/11/2/12
- mesenchymal stromal cell;
- gene expression;
Mesenchymal stromal cells (MSCs) are promising candidates for cell therapy. Their therapeutic use requires extensive expansion to obtain a sufficiently high number of cells for clinical applications. State-of-the-art expansion systems, that is, primarily culture flask-based systems, are limited regarding scale-up, automation, and reproducibility. To overcome this bottleneck, microcarrier (MC)-based expansion processes have been developed. For the first time, MSCs from the perinatal sources umbilical cord (UC) and amniotic membrane (AM) were expanded on MCs. This study focuses on the comparison of flask- and Cytodex 1 MC-expanded MSCs by evaluating the influence of the expansion process on biological MSC characteristics. Furthermore, we tested the hypothesis to obtain more homogeneous MSC preparations by expanding cells on MCs in controlled large-scale bioreactors. MSCs were extensively characterized determining morphology, cell growth, surface marker expression, and functional properties such as differentiation capacity, secretion of paracrine factors, and gene expression. Based on their gene expression profile MSCs from different donors and sources clearly clustered in distinct groups solely depending on the expansion process—MC or flask culture. MC- and flask-expanded MSCs significantly differed from each other regarding surface markers and both paracrine factors and gene expression profiles. Furthermore, based on gene expression analysis, MC cultivation of MSCs in controlled bioreactor systems resulted in less heterogeneity between cells from different donors. In conclusion, MC-based MSC expansion in controlled bioreactors has the potential to reliably produce MSCs with altered characteristics and functions as compared to flask-expanded MSCs. These findings may be useful for the generation of MSCs with tailored properties for clinical applications. Biotechnol. Bioeng. 2014;111: 2290–2302. © 2014 Wiley Periodicals, Inc.