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A novel automated bioreactor for scalable process optimisation of haematopoietic stem cell culture

Author:
Ratcliffe, E., Glen, K.E., Workman, V.L., Stacey, A.J., Thomas, R.J.
Source:
Journal of biotechnology 2012 v.161 no.3 pp. 387-390
ISSN:
0168-1656
Subject:
bioreactors, cell culture, cell proliferation, erythrocytes, manufacturing, monitoring, oxygen, stem cells, umbilical cord
Abstract:
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, 24×15mL 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 48h total media exchange protocol was established to be in the order of 10⁷cells/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.
Agid:
109046