Large-scale ex vivo generation of human neutrophils from cord blood CD34+ cells

Zhenwang Jie, Yu Zhang, Chen Wang, Bin Shen, Xin Guan, Zhihua Ren, Xinxin Ding, Wei Dai, Yongping Jiang

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2 Scopus citations

Abstract

Conventional high-dose chemotherapy frequently leads to severe neutropenia, during which patients experience a high risk of infection. Although support care with donor's neutrophils is possible this choice is largely hampered by the limited availability of matched donors. To overcome this problem, we explored a large-scale ex vivo production of neutrophils from hematopoietic stem cells (HSCs) using a four-stage culture approach in a roller-bottle production platform. We expanded CD34+ HSCs isolated from umbilical cord blood (UCB) using our in-house special medium supplemented with cytokine cocktails and achieved about 49000-fold expansion of cells, among which about 61% were differentiated mature neutrophils. Ex vivo differentiated neutrophils exhibited a chemotactic activity similar to those from healthy donors and were capable of killing E. coli in vitro. The expansion yield as reported herein was at least 5 times higher than any other methods reported in the literature. Moreover, the cost of our modified medium was only a small fraction (<1/60) of the Stem- Span™ SFEM. Therefore, our ex vivo expansion platform, coupled with a low cost of stem cell culture due to the use of a modified medium, makes large-scale manufacturing neutrophils possible, which should be able to greatly ameliorate neutrophil shortage for transfusion in the clinic.

Original languageEnglish (US)
Article numbere0180832
JournalPloS one
Volume12
Issue number7
DOIs
StatePublished - Jul 2017

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Jie, Z., Zhang, Y., Wang, C., Shen, B., Guan, X., Ren, Z., Ding, X., Dai, W., & Jiang, Y. (2017). Large-scale ex vivo generation of human neutrophils from cord blood CD34+ cells. PloS one, 12(7), [e0180832]. https://doi.org/10.1371/journal.pone.0180832