Clinical Scale Ex Vivo Manufacture of Neutrophils From Hematopoietic Progenitor Cells

Timmins, N.E., Palfreyman, E., Marturana, F., Dietmair, S., Luikenga, S., Lopez, G., Fung, Y.L., Minchinton, R. and Nielsen, L.K. (2009) Clinical Scale Ex Vivo Manufacture of Neutrophils From Hematopoietic Progenitor Cells. Biotechnology and Bioengineering, 104 4: 832-840. doi:10.1002/bit.22433

Author Timmins, N.E.
Palfreyman, E.
Marturana, F.
Dietmair, S.
Luikenga, S.
Lopez, G.
Fung, Y.L.
Minchinton, R.
Nielsen, L.K.
Title Clinical Scale Ex Vivo Manufacture of Neutrophils From Hematopoietic Progenitor Cells
Journal name Biotechnology and Bioengineering   Check publisher's open access policy
ISSN 0006-3592
Publication date 2009-11-01
Year available 2009
Sub-type Article (original research)
DOI 10.1002/bit.22433
Open Access Status DOI
Volume 104
Issue 4
Start page 832
End page 840
Total pages 9
Place of publication United States
Publisher John Wiley & Sons
Language eng
Subject C1
Abstract 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(+) H PC 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. Biotechnol. Bicieng. 2009;104: 832-840. (C) 2009 Wiley Periodicals, Inc.
Keyword cellular therapy
cell culture
clinical translation
hematopoietic progenitors
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID LP 0669698
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Australian Institute for Bioengineering and Nanotechnology Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 18 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 12 Nov 2009, 21:54:42 EST by Mr Andrew Martlew on behalf of Aust Institute for Bioengineering & Nanotechnology