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Title: Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
Authors: Moore, Rebecca L.L.
Worrallo, Matthew J.
Mitchell, Peter D.
Harriman, Jon
Glen, Katie E.
Thomas, Robert James
Keywords: Cell culture
Delta-like 1
Ex vivo expansion
Hematopoietic progenitor cell
Immobilised
Manufacturing
Notch
Scalable
Issue Date: 2017
Publisher: BioMed Central / © The Authors
Citation: MOORE, R.L.L. ... et al, 2017. Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor. BMC Biotechnology, 17, article 65.
Abstract: BACKGROUND: Umbilical cord blood provides a source of hematopoietic stem cells for transplantation with immunological and availability advantages over conventional bone marrow sources. Limited cell numbers and slower engraftment from umbilical cord blood units has led to the clinical development of immobilised Notch ligand Delta-Like 1 to promote ex vivo expansion of a rapidly engrafting cell population. However, current immobilisation methods are not simple to scale in a controlled manner. RESULTS: Delta-Like 1 was immobilised onto streptavidin coated magnetic particles via a heterobifunctionalised polyethylene glycol linker molecule to provide an easily manipulated format of surface protein presentation. CD34(+) enriched cord blood cells were treated with Delta-Like 1 immobilised particles, and immunophenotypic markers measured to monitor population distributions using cluster identification, characterization, and regression software. The amenability of the approach to scalability was evaluated in a micro-scale stirred tank bioreactor. Surface concentration of Delta-Like 1 was well controlled used differing stoichiometric reagent ratios. Protein immobilisation was a cost effective process and particles were efficiently removed from the final cell product. Immobilised Delta-Like 1 is functional and stimulates qualitatively similar CD34(hi), CD38(lo), CD90(lo), CD133(hi), CD135(hi) progenitor expansion in both static culture and scalable stirred culture platforms. CONCLUSIONS: Immobilised Delta-Like 1 in this form has the potential to improve the manufacturing efficiency and control of final ex vivo expanded cell product through compatibility with highly controlled and characterised suspension culture systems.
Description: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor: This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), [grant number: EP/K00705X/1].
Version: Published
DOI: 10.1186/s12896-017-0383-0
URI: https://dspace.lboro.ac.uk/2134/26082
Publisher Link: http://dx.doi.org/10.1186/s12896-017-0383-0
Appears in Collections:Published Articles (Mechanical, Electrical and Manufacturing Engineering)

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