Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells

N E Timmins; E Palfreyman; F Marturana; S Dietmair; S Luikenga; G H Lopez; Yoke Lin Fung; R Minchinton; L K Nielsen

doi:10.1002/bit.22433

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Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells

Journal article

Peer reviewed

Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells

N E Timmins, E Palfreyman, F Marturana, S Dietmair, S Luikenga, G H Lopez, Yoke Lin Fung, R Minchinton and L K Nielsen

Biotechnology and Bioengineering, Vol.104(4), pp.832-840

2009

DOI: https://doi.org/10.1002/bit.22433

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Abstract

cellular therapy

CD34þ

cell culture

clinical translation

neutrophils

hematopoietic progenitors

Dose-intensive chemotherapy results in an obligatory period of severe neutropenia during which patients are at high risk of infection. While patient support with donor neutrophils is possible, this option is restricted due to donor availability and logistic complications. To overcome these problems, we explored the possibility of large scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells (HPC). CD34+ HPC isolated from umbilical cord blood (UCB) and mobilized peripheral blood (mPB) were expanded in serum-free medium supplemented with stem cell factor, granulocyte colony stimulating factor, and a thrombopoietin peptide mimetic. After 15 days of cultivation a 5,800-fold expansion in cell number was achieved for UCB, and up to 4,000-fold for mPB, comprising 40% and 60% mature neutrophils respectively. Ex vivo expanded neutrophils exhibited respiratory burst activity similar to that for donor neutrophils, and were capable of killing Candida albicans in vitro. These yields correspond to a more than 10-fold improvement over current methods, and are sufficient for the production of multiple neutrophil transfusion doses per HPC donation. To enable clinical scale manufacture, we adapted our protocol for use in a wave-type bioreactor at a volume of 10 L. This is the first demonstration of a large scale bioprocess suitable for routine manufacture of a mature blood cell product from HPC, and could enable prophylactic neutrophil support for chemotherapy patients. © 2009 Wiley Periodicals, Inc.

Details

Title: Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells
Authors: N E Timmins (Author) - University of Queensland
E Palfreyman (Author) - University of Queensland
F Marturana (Author) - University of Queensland
S Dietmair (Author) - University of Queensland
S Luikenga (Author) - University of Queensland
G H Lopez (Author) - Australian Red Cross Blood Services
Yoke Lin Fung (Author) - Australian Red Cross Blood Services
R Minchinton (Author) - Australian Red Cross Blood Services
L K Nielsen (Author) - University of Queensland
Publication details: Biotechnology and Bioengineering, Vol.104(4), pp.832-840
Publisher: John Wiley & Sons Inc.
Date published: 2009
DOI: 10.1002/bit.22433
ISSN: 0006-3592
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99448979702621
Output Type: Journal article

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Web Of Science research areas: Biotechnology & Applied Microbiology

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