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

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.

SUBMITTER: Jie Z

PROVIDER: S-EPMC5507460 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Jie Zhenwang Z Zhang Yu Y Wang Chen C Shen Bin B Guan Xin X Ren Zhihua Z Ding Xinxin X Dai Wei W Jiang Yongping Y

PloS one 20170711 7

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 isola ...[more]

PMID: 28700636

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Project description:Diabetes can impair wound closure, which can give rise to major clinical problems. Most treatments for wound repair in diabetes remain ineffective. This study aimed to investigate the influence on wound closure of treatments using expanded human cord blood CD34(+) cells (CB-CD34(+) cells), freshly isolated CB-CD34(+) cells and a cytokine cocktail. The test subjects were mice with streptozotocin-induced diabetes. Wounds treated with fresh CB-CD34(+) cells showed more rapid repair than mice given the PBS control. Injection of expanded CB-CD34(+) cells improved wound closure significantly, whereas the injection of the cytokine cocktail alone did not improve wound repair. The results also demonstrated a significant decrease in epithelial gaps and advanced re-epithelialization over the wound bed area after treatment with either expanded CB-CD34(+) cells or freshly isolated cells compared with the control. In addition, treatments with both CB-CD34(+) cells and the cytokine cocktail were shown to promote recruitment of CD31(+)-endothelial cells in the wounds. Both the CB-CD34(+) cell population and the cytokine treatments also enhanced the recruitment of CD68-positive cells in the early stages (day 3) of treatment compared with PBS control, although the degree of this enhancement was found to decline in the later stages (day 9). These results demonstrated that expanded CB-CD34(+) cells or freshly isolated CB-CD34(+) cells could accelerate wound repair by increasing the recruitment of macrophages and capillaries and the reepithelialization over the wound bed area. Our data suggest an effective role in wound closure for both ex vivo expanded CB-CD34(+) cells and freshly isolated cells, and these may serve as therapeutic options for wound treatment for diabetic patients. Wound closure acceleration by expanded CB-CD34(+) cells also breaks the insufficient quantity obstacle of stem cells per unit of cord blood and other stem cell sources, which indicates a broader potential for autologous transplantation.

Dataset Information

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

Publications

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

Similar Datasets

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