Large-scale ex vivo generation of human neutrophils from cord blood CD34+ cells
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Authors
Jie, Zhenwang
Zhang, Yu
Wang, Chen
Shen, Bin
Guan, Xin
Ren, Zhihua
Ding, Xinxin
Dai, Wei
Jiang, Yongping
Issue Date
2017-07-11
Type
Article
Language
en_US
Keywords
antigens , CD34+ , cell differentiation , fetal blood , hematopoietic stem cells (HSCs) , neutrophils , umbilical cord blood (UCB) , neutropenia
Alternative Title
PLoS ONE
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 StemSpan™ 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.
Description
Citation
Jie, Z., Zhang, Y., Wang, C., Shen, B., Guan, X., Ren, Z., . . . Jiang, Y. (2017). Largescale ex vivo generation of human neutrophils from cord blood CD34+ cells. PLoS ONE, 12(7), 1-18. doi:10.1371/journal.pone.0180832
Publisher
PLoS ONE
License
Journal
Volume
Issue
PubMed ID
DOI
ISSN
1932-6203