Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.

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...

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Main Authors:	Rebecca Moore, Matthew J. Worrallo, Peter D. Mitchell, Jon Harriman, Katie Glen, Rob Thomas
Format:	Default Article
Published:	2017
Subjects:	Mechanical engineering not elsewhere classified Cell culture Delta-like 1 Ex vivo expansion Hematopoietic progenitor cell Immobilised Manufacturing Notch Scalable Mechanical Engineering not elsewhere classified
Online Access:	https://hdl.handle.net/2134/26082
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id	rr-article-9564008
record_format	Figshare
spelling	rr-article-95640082017-08-04T00:00:00Z Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor. Rebecca Moore (1253241) Matthew J. Worrallo (7201355) Peter D. Mitchell (7129847) Jon Harriman (4334050) Katie Glen (1255023) Rob Thomas (1249266) Mechanical engineering not elsewhere classified Cell culture Delta-like 1 Ex vivo expansion Hematopoietic progenitor cell Immobilised Manufacturing Notch Scalable Mechanical Engineering not elsewhere classified 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. 2017-08-04T00:00:00Z Text Journal contribution 2134/26082 https://figshare.com/articles/journal_contribution/Immobilisation_of_Delta-like_1_ligand_for_the_scalable_and_controlled_manufacture_of_hematopoietic_progenitor_cells_in_a_stirred_bioreactor_/9564008 CC BY 4.0
institution	Loughborough University
collection	Figshare
topic	Mechanical engineering not elsewhere classified Cell culture Delta-like 1 Ex vivo expansion Hematopoietic progenitor cell Immobilised Manufacturing Notch Scalable Mechanical Engineering not elsewhere classified
spellingShingle	Mechanical engineering not elsewhere classified Cell culture Delta-like 1 Ex vivo expansion Hematopoietic progenitor cell Immobilised Manufacturing Notch Scalable Mechanical Engineering not elsewhere classified Rebecca Moore Matthew J. Worrallo Peter D. Mitchell Jon Harriman Katie Glen Rob Thomas Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
description	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.
format	Default Article
author	Rebecca Moore Matthew J. Worrallo Peter D. Mitchell Jon Harriman Katie Glen Rob Thomas
author_facet	Rebecca Moore Matthew J. Worrallo Peter D. Mitchell Jon Harriman Katie Glen Rob Thomas
author_sort	Rebecca Moore (1253241)
title	Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
title_short	Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
title_full	Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
title_fullStr	Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
title_full_unstemmed	Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
title_sort	immobilisation of delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.
publishDate	2017
url	https://hdl.handle.net/2134/26082
_version_	1797555730895601664

Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.

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