Journal
JOURNAL OF BIOTECHNOLOGY
Volume 161, Issue 3, Pages 387-390Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jbiotec.2012.06.025
Keywords
Haematopoietic stem cells; Suspension culture, Bioreactor; Cell culture automation; Process development
Categories
Funding
- Celgene Cellular Therapeutics via the US Defense Advanced Research Projects Agency (DARPA)
- Defense Sciences Office (DSO) Blood Pharming programme [FA9550-08-1-0392]
- EPSRC [EP/H028277/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/H028277/1] Funding Source: researchfish
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Proliferation and differentiation of haematopoietic stem cells (HSCs) from umbilical cord blood at large scale will potentially underpin production of a number of therapeutic cellular products in development, including erythrocytes and platelets. However, to achieve production processes that are scalable and optimised for cost and quality, scaled down development platforms that can define process parameter tolerances and consequent manufacturing controls are essential. We have demonstrated the potential of a new, automated, 24 x 15 mL replicate suspension bioreactor system, with online monitoring and control, to develop an HSC proliferation and differentiation process for erythroid committed cells (CD71(+), CD235a(+)). Cell proliferation was relatively robust to cell density and oxygen levels and reached up to 6 population doublings over 10 days. The maximum suspension culture density for a 48 h total media exchange protocol was established to be in the order of 10(7) cells/mL. This system will be valuable for the further HSC suspension culture cost reduction and optimisation necessary before the application of conventional stirred tank technology to scaled manufacture of HSC derived products. (C) 2012 Elsevier B.V. All rights reserved.
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