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Title: Immobilized hematopoietic growth factors onto magnetic particles offer a scalable strategy for cell therapy manufacturing in suspension cultures
Authors: Worrallo, Matthew J.
Moore, Rebecca L.L.
Glen, Katie E.
Thomas, Robert James
Keywords: Growth factors
Hematopoietic
Immobilized
Manufacturing
Scalable
Issue Date: 2017
Publisher: © The Authors. Published by Wiley
Citation: WORRALLO, M.J., 2017. Immobilized hematopoietic growth factors onto magnetic particles offer a scalable strategy for cell therapy manufacturing in suspension cultures. Biotechnology Journal, 12 (2), article 1600493.
Abstract: Hematopoietic therapies require high cell dosages and precise phenotype control for clinical success; scalable manufacturing processes therefore need to be economic and controllable, in particular with respect to culture medium and growth factor (GF) strategy. The aim of this work was to demonstrate the biological function, and integration within scalable systems, of a highly controllable immobilized growth factor (iGF) approach. GFs were biotinylated and attached to streptavidin coated magnetic particles. GF concentration during biotinylation, GF-biotin ratio, and GF lysine content were shown to control iGF surface concentration and enable predictable co-presentation of multiple GF on a single bead. Function was demonstrated for immobilized GMCSF, SCF, TPO and IL-3 in GF dependent cell lines TF-1 and M-07e. Immobilized GMCSF (iGMCSF) was analyzed to show sustained activity over eight days of culture, a two to three order of magnitude potency increase relative to soluble factor, and retained functionality under agitation in a microscale stirred tank bioreactor. Further, short exposure to iGMCSF demonstrated prolonged growth response relative to soluble factor. This immobilization approach has the potential to reduce the manufacturing costs of scaled cell therapy products by reducing GF quantities and offers important process control opportunities through separation of GF treatments from the bulk media.
Description: This is an Open Access Article. It is published by Wiley under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/
Version: Published
DOI: 10.1002/biot.201600493
URI: https://dspace.lboro.ac.uk/2134/23658
Publisher Link: http://dx.doi.org/10.1002/biot.201600493
ISSN: 1860-6768
Appears in Collections:Published Articles (Mechanical, Electrical and Manufacturing Engineering)

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