CD26 Inhibition on CD34+ or Lineage− Human Umbilical Cord Blood Donor HSC/HPC Improves Long-Term Engraftment into NOD/SCID/Beta2null Immunodeficient Mice

• Published in: Blood Vol. 110; no. 11; p. 4853
• Main Authors: Christopherson, Kent W., Paganessi, Laura A., Napier, Stephanie, Porecha, Nehal K.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 16.11.2007
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V110.11.4853.4853

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.