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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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
Externally publishedYes

Fingerprint

blood cells
Stem cells
Fetal Blood
neutrophils
Blood Cells
Neutrophils
Blood
Cell culture
Production platforms
Chemotherapy
Tissue Donors
Bottles
Hematopoietic Stem Cells
Escherichia coli
Costs
Availability
Cytokines
Costs and Cost Analysis
neutropenia
umbilical cord

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., ... 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

Large-scale ex vivo generation of human neutrophils from cord blood CD34+ cells. / Jie, Zhenwang; Zhang, Yu; Wang, Chen; Shen, Bin; Guan, Xin; Ren, Zhihua; Ding, Xinxin; Dai, Wei; Jiang, Yongping.

In: PloS one, Vol. 12, No. 7, e0180832, 07.2017.

Research output: Contribution to journalArticle

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, vol. 12, no. 7, e0180832. https://doi.org/10.1371/journal.pone.0180832
Jie, Zhenwang ; Zhang, Yu ; Wang, Chen ; Shen, Bin ; Guan, Xin ; Ren, Zhihua ; Ding, Xinxin ; Dai, Wei ; Jiang, Yongping. / Large-scale ex vivo generation of human neutrophils from cord blood CD34+ cells. In: PloS one. 2017 ; Vol. 12, No. 7.
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