Journal
BLOOD
Volume 116, Issue 19, Pages 3999-4006Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-03-276212
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Funding
- Gabrielle's Angel Foundation for Cancer Research
- Memorial Sloan-Kettering Cancer Center Society
- Translational and Integrative Medicine Research
- National Cancer Institute, National Institutes of Health [P01 CA23766]
- Gar Reichman Fund of the Cancer Research Institute
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Double-unit cord blood transplantation (DCBT) appears to enhance engraftment despite sustained hematopoiesis usually being derived from a single unit. To investigate DCBT biology, in vitro and murine models were established using cells from 39 patient grafts. Mononuclear cells (MNCs) and CD34(+) cells from each unit alone and in DCB combination were assessed for colony-forming cell and cobblestone area-forming cell potential, and multilineage engraftment in NOD/SCID/IL2R-gamma(null) mice. In DCB assays, the contribution of each unit was measured by quantitative short tandem repeat region analysis. There was no correlation between colony-forming cell (n = 10) or cobblestone area-forming cell (n = 9) numbers and clinical engraftment, and both units contributed to DCB cocultures. In MNC transplantations in NOD/SCID/IL2R-gamma(null) mice, each unit engrafted alone, but MNC DCBT demonstrated single-unit dominance that correlated with clinical engraftment in 18 of 21 cases (86%, P < .001). In contrast, unit dominance and clinical correlation were lost with CD34(+) DCBT (n = 11). However, add-back of CD34(-) to CD34(+) cells (n = 20) restored single-unit dominance with the dominant unit correlating not with clinical engraftment but also with the origin of the CD34(-) cells in all experiments. Thus, unit dominance is an in vivo phenomenon probably associated with a graft-versus-graft immune interaction mediated by CD34(-) cells. (Blood. 2010; 116(19):3999-4006)
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