4.7 Article

Combination of HOXB4 and Delta-1 ligand improves expansion of cord blood cells

Journal

BLOOD
Volume 116, Issue 26, Pages 5859-5866

Publisher

AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-05-286062

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Funding

  1. National Institutes of Health [R01HL08434, R01HL080245, R24HL074445, P30DK056465]
  2. Damon Runyon Cancer Research Foundation [35-07]
  3. Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research

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Umbilical cord blood (UCB) is an attractive cell source for hematopoietic cell transplantation (HCT). Here we examine whether the combination of homeobox B4 (HOXB4) and Delta-1 ligand (DL) synergize when used together. Monkey and human UCB CD34(+) cells were transduced with a HOXB4-expressing gammaretroviral vector and cultured with DL. Individual and combined effects of HOXB4 and DL were assessed by colony-forming unit assays, flow cytometry, and nonobese diabetic/severe combined immune deficienct mouse transplantation. The presence of DL yielded higher percentage of CD34(+) and CD7(+) cells and lower percentages of CD14(+) cells than non-DL cultures. Furthermore, HOXB4 yielded higher percentages of CD34(+) and CD14(+) cells than non-HOXB4 cultures. Interestingly, coculture with DL-expressing OP9 cells resulted in better maintenance of HOXB4 than culture in DL-conditioned medium. Culture of HOXB4-transduced human cells in the presence of DL yielded enhanced generation of repopulating cells with higher levels of engraftment of human CD45(+), CD34(+), CD3(+), CD20(+), and CD41(+) cells compared with either factor individually. Our results demonstrate enhanced generation of hematopoietic progenitors by combining HOXB4 and DL; addition of DL further enhances expansion of multipotent cells capable of repopulating lymphoid and megakaryocyte lineages, which is not observed with HOXB4 alone. (Blood. 2010;116(26):5859-5866)

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