Process development of human mesenchymal stem cell microcarrier culture using a single-use automated microbioreactor platform
May 7-10, 2017
Improvements to process development technology will have a significant impact in reducing the overall costs associated with the manufacture and scale-up of human cell-based therapies. Single-use, small-scale models, including microbioreactors, play a critical role in this regard as they reduce reagent requirements and can facilitate high-throughput screening of process parameters and culture conditions. Here we have demonstrated, for the first time, the amenability of the automated ambr15 cell culture single-use, microbioreactor system (originally designed for free suspension culture) for adherent hMSC microcarrier culture. We also demonstrated that the ambr15 could be used for bioprocess development of a microcarrier process which was subsequently validated with larger-scale single-use spinner flask studies. The results were achieved by a combination of strategies including adapting the free suspension design of the vessel to improve the suspension and mixing of the microcarriers. A more effective cell attachment method was also developed by using only 50% of the final working volume of medium for the first 24 h combined with an intermittent agitation strategy. These improvements led to a reduction in the initial lag phase which in turn resulted in > 150 % increase in viable cell density after 24 h compared to the original process (no agitation for 24 h and 100 % working volume). Using the same methodology as in the ambr 15, similar improvements were obtained in larger scale spinner flask studies.
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Qasim A. Rafiq, "Process development of human mesenchymal stem cell microcarrier culture using a single-use automated microbioreactor platform" in "Single-use Technologies II: Bridging Polymer Science to Biotechnology Applications", kta Mahajan (Genentech, Inc., USA) Gary Lye (University College London, UK) Regine Eibl-Schindler (Zurich University of Applied Science, Switzerland) Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/biopoly_ii/6