title: 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.
abstract: 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.
authors.affiliation: Sections of Hematology and Stem Cell Transplantation, Division of Hematology, Department of Internal Medicine, Chicago, IL 60612, USA.
authors.forename: Kent W
authors.initials: KW
authors.lastname: Christopherson
authors.forename: Laura A
authors.initials: LA
authors.lastname: Paganessi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Napier
authors.forename: Nehal K
authors.initials: NK
authors.lastname: Porecha
mesh_terms: 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*
chemical_list: D018952:Antigens, CD34; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009842:Oligopeptides; D001613:beta 2-Microglobulin; C041445:diprotin A; D018819:Dipeptidyl Peptidase 4