title: Keratinocyte growth factor and stem cell factor to improve thymopoiesis after autologous CD34+ cell transplantation in rhesus macaques.
abstract: Deficient thymopoiesis and retarded recovery of naive CD4(+) T cells are important determinants of insufficient immune-competence following hematopoietic stem cell transplantation (HSCT). Although keratinocyte growth factor (KGF) may protect the thymic epithelium, stem cell factor (SCF) is involved in early thymopoiesis. We evaluated whether KGF alone or combined with SCF would affect thymopoiesis and hematologic recovery following myeloablative autologous HSCT into rhesus macaques. Purpose-bred adult rhesus macaques received 10(6) autologous CD34(+)-selected mononuclear bone marrow cells (BMC)/kg after 9 Gy myeloablative conditioning. Animals were treated with phosphate-buffered saline (PBS) (n = 2), KGF alone (n = 2), or KGF combined with SCF (n = 2). KGF-treated animals showed accelerated hematologic recovery, improved thymopoiesis, and enhanced naive T-cell recovery following transplantation. Improved T cell recovery was not associated with protection against cytomegalovirus reactivation nor with improved antibody response to tetanus toxoid vaccination. Animals treated with KGF and SCF experienced severe adverse events that precluded evaluation of thymopoiesis and T cell recovery. Collectively, our data confirm that KGF may enhance thymopoiesis.
authors.affiliation: Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Wils
authors.forename: Fatima S F
authors.initials: FS
authors.lastname: Aerts-Kaya
authors.forename: Elwin J C
authors.initials: EJ
authors.lastname: Rombouts
authors.forename: Irene
authors.initials: I
authors.lastname: van Mourik
authors.forename: Anita
authors.initials: A
authors.lastname: Rijken-Schelen
authors.forename: Trudi P
authors.initials: TP
authors.lastname: Visser
authors.forename: Eric
authors.initials: E
authors.lastname: Braakman
authors.forename: Gerard
authors.initials: G
authors.lastname: Wagemaker
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000276:immunology; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008253:Macaca mulatta; D008297:Male; D019089:Stem Cell Factor / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D019089:Stem Cell Factor; D051523:Fibroblast Growth Factor 7