Abstract：
: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.
journal_name
Bloodjournal_title
Bloodauthors
Watts KL,Delaney C,Humphries RK,Bernstein ID,Kiem HPdoi
10.1182/blood-2010-05-286062subject
Has Abstractpub_date
2010-12-23 00:00:00pages
5859-66issue
26eissn
0006-4971issn
1528-0020pii
blood-2010-05-286062journal_volume
116pub_type
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