title: Keratinocyte growth factor enhanced immune reconstitution in murine allogeneic umbilical cord blood cell transplant.
abstract: Umbilical cord blood (UCB) is used increasingly as a source of hematopoietic cells because of a lower risk of graft-versus-host disease (GVHD). Myeloablative conditioning before allogeneic umbilical cord blood transplant (allo-UCBT) results in thymic epithelial cell injury and T-cell immune deficiency. Full-term fetal blood cells were used as hematopoietic cells in a previous murine allo-UCBT model with a limited number of mice surviving the myeloablative conditioning. We designed a viable murine allo-UCBT protocol with platelet concentrate support. Keratinocyte growth factor (KGF) is a mitogen of thymic epithelial cells that promotes recovery of thymic epithelium when given before total body irradiation (TBI)-containing conditioning in experimental murine models. We hypothesized that KGF pre-administration would improve post-allo-UCBT thymopoiesis. To test this hypothesis, allo-UCBT recipient mice were given KGF or control saline prior to UCBT. Platelet concentrate support significantly improved the survival rate of murine allo-UCBT recipients. KGF administration significantly increased donor-derived T and natural killer T (NKT) cells at day +35 in spleens of allo-UCBT recipients. KGF administration also improved thymic function after allo-UCBT, resulting in higher copies of signal joint T-cell receptor rearrangement excision circles (sjTRECs) in splenocytes. Finally, we found that KGF pre-administration could enhance the graft-versus-leukemia effect. In conclusion, KGF can be administered safely to recipients of allo-UCBT to enhance T-cell immune reconstitution.
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, the First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Guanghua
authors.initials: G
authors.lastname: Chen
authors.forename: Shumin
authors.initials: S
authors.lastname: Qiao
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.forename: Aining
authors.initials: A
authors.lastname: Sun
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D009368:Neoplasm Transplantation; D017713:Platelet Transfusion; D011247:Pregnancy; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D051523:Fibroblast Growth Factor 7