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Enhanced engraftment of umbilical cord blood-derived stem cells in NOD/SCID mice by cotransplantation of a second unrelated cord blood unit.

Nauta AJ, Kruisselbrink AB, Lurvink E, Mulder A, Claas FH, Noort WA, Willemze R, Fibbe WE

Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands. nauta@lumc.nl

OBJECTIVE: Umbilical cord blood (UCB) is considered as an attractive alternative source of hematopoietic stem cells for allogeneic stem cell transplantations in patients who lack human leukocyte antigen (HLA)-matched donors. However, the low cell dose adversely affects hematopoietic recovery and therefore limits application of UCB transplantation in adults. Transplantation of multiple UCB units could be a strategy to overcome cell dose limitations. MATERIALS AND METHODS: To investigate the effect of double cord transplantation, nonobese diabetic/severe combined immunodeficient mice were transplanted with human hematopoietic progenitor cells (CD34(+)) derived from two UCB units with HLA disparity. Human cell engraftment and donor origin was determined by flow cytometry. RESULTS: Double CB transplantation resulted in increased engraftment levels in the bone marrow and peripheral blood in comparison with recipients of a single unit. Because this effect could be due to the higher cell dose (2.10(5) vs 1.10(5) cells), double CB transplantation was compared with single units containing equal cell numbers (2.10(5)). In some cases, engraftment levels in recipients of single units containing 2.10(5) cells were significantly higher than after transplantation of 1.10(5) cells. These engraftment levels were similar to those observed after double CB transplantation. Chimerism analysis indicated that increased engraftment in recipients of two units was predominantly derived from one unit, whereas in other cases the contribution of the two units was similar. CONCLUSION: These results indicate that engraftment may be enhanced by addition of a second unrelated CB that might be attributed to a cell dose effect or due to a graft-facilitating effect.

Published 12 October 2005 in Exp Hematol, 33(10): 1249-56.
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