Preservation of G-CSF mobilized whole blood in an automated closed hollow-fiber bioreactor system

Kreuk, A. M. De; Zevenbergen, Adri; Jonuleit, Tarja; Schuurhuis, Gerrit Jan; Huijgens, Peter C.; Hendriks, E. C. M.; Oostveen, J. W. Van; Lemke, Horst‐Dieter; Jonkhoff, A. R.

doi:10.1080/14653240410004952

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…Stirred cultures were shown to have equal or better performance compared to static flask cultures, and could be operated at higher cell densities (Collins et al, 1998b). Other bioreactor configurations employed for the cultivation of HPC include flat bed perfusion devices (Jaroscak et al, 2003;Koller et al, 1998;Palsson et al, 1993;Sandstrom et al, 1996Sandstrom et al, , 1995, hollow fiber perfusion devices (de Kreuk et al, 2004;Knazek et al, 1990;Malone et al, 2001;Sardonini and Wu, 1993), rotating wall vessels (Liu et al, 2006), and airlift reactors (Sardonini and Wu, 1993).…”

Section: Discussionmentioning

confidence: 97%

Clinical scale ex vivo manufacture of neutrophils from hematopoietic progenitor cells

Timmins

Palfreyman

Marturana

et al. 2009

Biotech & Bioengineering

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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.

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