Packed bed bioreactor for the isolation and expansion of placental-derived mesenchymal stromal cells
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Date
2015
Authors
Osiecki, M.
Michl, T.D.
Babur, B.K.
Kabiri, M.
Atkinson, K.
Lott, W.B.
Griesser, H.J.
Doran, M.
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Kerkis, I.
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Journal article
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PLoS ONE, 2015; 10(2):1-18
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Abstract
Large numbers of Mesenchymal stem/stromal cells (MSCs) are required for clinical relevant doses to treat a number of diseases. To economically manufacture these MSCs, an automated bioreactor system will be required. Herein we describe the development of a scalable closed-system, packed bed bioreactor suitable for large-scale MSCs expansion. The packed bed was formed from fused polystyrene pellets that were air plasma treated to endow them with a surface chemistry similar to traditional tissue culture plastic. The packed bed was encased within a gas permeable shell to decouple the medium nutrient supply and gas exchange. This enabled a significant reduction in medium flow rates, thus reducing shear and even facilitating single pass medium exchange. The system was optimised in a small-scale bioreactor format (160 cm(2)) with murine-derived green fluorescent protein-expressing MSCs, and then scaled-up to a 2800 cm(2) format. We demonstrated that placental derived MSCs could be isolated directly within the bioreactor and subsequently expanded. Our results demonstrate that the closed system large-scale packed bed bioreactor is an effective and scalable tool for large-scale isolation and expansion of MSCs.
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Copyright 2015 Osiecki et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. (https://creativecommons.org/licenses/by/4.0/)