Abstract
Umbilical cord blood (UCB) is a source of stem cells for hematopoietic transplantation (
Laughlin, et al.
) but application in adults is limited by marginal stem cell numbers. Combining cord blood units has shown promise in achieving engraftment (NEJM
2004
; 351
:2265
Barker, et al.
) without crossed immunologic rejection. Short-term hematopoiesis showed contributions from both cords, but long-term engraftment derived predominantly from just one cord. To study this process we have developed an in vivo pre-clinical competitive repopulation assay using NOD-scid IL-2rγnull mice that support high levels of human UCB engraftment (Blood
2002
; 100
:41a
[abs #142]Shultz, et al,
). NOD-scid IL-2rγnull mice were transplanted with T-cell depleted UCB containing 3x104 HLA-A2+ CD34+ cells, 3x104 HLA-A2− CD34+ cells, or a 1:1 mixture (6x104 CD34+ cells). Human hematopoietic chimerism, measured by human CD45 and HLA-A2 expression, was quantified in bone marrow 6 and 12 weeks after transplantation. Variable mixed engraftment within individual as well as between 6 separate experiments was observed. At both 6 and 12 weeks, mixed contribution from both cords was achieved although rarely in a 1:1 ratio despite the infusion of equivalent CD34+ cell numbers. HLA-A2 expression did not provide a selective advantage. The complete dominance of one cord observed in the clinical report and in animal studies (J. Immunol.
2005
, 174
:6477
Yahata, et al.
) suggests an important role for the immune activity of UCB T-cells in this competitive process, a hypothesis we are currently testing. This model has a rapid turnaround and can test multiple permutations, providing a preclinical vehicle for characterizing optimal combinations of cord cells and for testing conditions that allow one cord to ultimately prevail.Molecular Therapy
2004
; 10
: 882
Legend: Engraftment of human CD45+ cells at 6 weeks. All bars represent single mice except for the HLA-A2+ group, which is the average (±SEM) of 3 mice.
Legend: Engraftment of human CD45+ cells at 6 weeks. All bars represent single mice except for the HLA-A2+ group, which is the average (±SEM) of 3 mice.
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