title: A novel automated bioreactor for scalable process optimisation of haematopoietic stem cell culture.
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, 24×15 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.
authors: Healthcare Engineering Research Group, Centre for Biological Engineering, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, Leicestershire, LE11 3TU, United Kingdom.
authors: E
authors: E
authors: Ratcliffe
authors: K E
authors: KE
authors: Glen
authors: V L
authors: VL
authors: Workman
authors: A J
authors: AJ
authors: Stacey
authors: R J
authors: RJ
authors: Thomas
mesh_terms: D001331:Automation; D019149:Bioreactors; D002452:Cell Count; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D010100:Oxygen / Q000494:pharmacology
chemical_list: D010100:Oxygen