Abstract: |
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-γnull 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-γnull 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, addback 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. © 2010 by The American Society of Hematology. |
Keywords: |
adolescent; adult; child; clinical article; preschool child; school child; aged; child, preschool; middle aged; young adult; human cell; nonhuman; animal cell; mouse; animals; mice; animal experiment; in vivo study; cell differentiation; models, animal; cord blood stem cell transplantation; engraftment; hematologic neoplasms; tissue donors; mononuclear cell; leukocytes, mononuclear; infant; transplantation, heterologous; hematopoiesis; colony-forming units assay; antigens, cd34; cd34 selection; experimental model; colony forming cell; short tandem repeat; graft enhancement, immunologic
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