CD26 inhibition on CD34+ or lineage- human umbilical cord blood donor hematopoietic stem cells/hematopoietic progenitor cells improves long-term engraftment into NOD/SCID/Beta2null immunodeficient mice.
Given the tremendous need for and potential of umbilical cord blood (CB) to be utilized as a donor source for hematopoietic stem cell (HSC) transplantation in adults, there is a strong push to overcome the constraints created by the limited volumes and subsequent limited HSC and hematopoietic progenitor cell (HPC) numbers available for HSC 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 HSCs and HPCs into a mouse recipient. To study the use of CD26 inhibitors as a method of improving the transplantation of human CB HSCs and HPCs, we utilized the nonobese diabetic/severe combined immunodeficient/beta 2 microglobulin null (NOD/SCID/B2m(null)) immunodeficient mouse model of HSC transplantation. We report here significant improvements in the engraftment of long-term repopulating cells following the treatment of either CD34(+) or lineage negative (lin()) donor CB with the CD26 inhibitor, Diprotin A, prior to transplant. These results establish a basis on which to propose the use of CD26 inhibitor treatment of donor CB units prior to transplantation for the purpose of improving transplant efficiency and subsequently patient outcome.
Christopherson
Kent W
KW
Sections of Hematology and Stem Cell Transplantation, Division of Hematology, Department of Internal Medicine, Chicago, IL 60612, USA.
Paganessi
Laura A
LA
Napier
Stephanie
S
Porecha
Nehal K
NK
D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D019070:Cell Lineage; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005312:Fetal Blood / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009842:Oligopeptides / Q000378:metabolism; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism*
D018952:Antigens, CD34; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009842:Oligopeptides; D001613:beta 2-Microglobulin; C041445:diprotin A; D018819:Dipeptidyl Peptidase 4