Given the tremendous need for and potential of umbilical cord blood to be utilized as a donor source for hematopoietic stem cell transplantation in adults, there is a strong push to overcome the constraints created by the limited volumes and subsequent limited hematopoietic stem and progenitor cell numbers available for hematopoietic stem cell transplantation from a single collection. We have previously described the use of CD26 inhibitor treatment of donor cells as a method to increase the transplant efficiency of mouse hematopoietic stem and progenitor cells into a mouse recipient (

Christopherson, KW 2nd, et al,
Science
2004
.
305
:
1000
–1003
). We therefore hypothesized that inhibition of CD26 on human donor cord blood prior to transplant would result in an increase in long-term engraftment potential. To test this hypothesis, we isolated CD34 enriched (CD34+) or lineage depleted (lin−) pooled cord blood cells, evaluated their level of CD26 expression and activity, and then tested their ability to engraft into the NOD/SCID/B2mnull immunodeficient mouse model of hematopoietic stem cell transplantation with or without prior CD26 inhibitor treatment. We observed that long-term engraftment into the recipient mouse bone marrow at twelve weeks post sub-lethal irradiation (350cGy), followed by transplantation of 1x105 pooled donor cells was 13.4±2.0% and 55.5±4.0% CD45+ human cells in the untreated, and CD26 inhibitor (Diprotin A) treated CD34+ donor cells respectively. We also observed engraftment levels in the mouse recipient bone marrow of 6.2±0.7% and 47.0±2.8% CD45+ human cells for untreated and CD26 inhibitor treated lin− cells respectively. These measurements represent approximately a 4-fold and 7.5-fold improvement in the engraftment of long-term repopulating cells resulting from CD26 inhibitor treatment of either CD34+ or lin− donor cells respectively. These pre-clinical results establish a basis on which to propose the use of CD26 inhibitor treatment of donor cord blood units prior to transplantation for the purpose of improving transplant efficiency and subsequently patient outcome.

Topics:
cd34 antigens, dipeptidyl-peptidase iv, donors, engraftment, immunologic deficiency syndromes, mice, severe combined immunodeficiency, umbilical cord blood, transplantation, hematopoietic stem cell transplantation

Author notes

Disclosure:Consultancy: Consultant for America Stem Cell, Inc., Carlsbad, California 92008.

2007, The American Society of Hematology
2007
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