title: Thrombopoietin augments ex vivo expansion of human cord blood-derived hematopoietic progenitors in combination with stem cell factor and flt3 ligand.
abstract: We studied the effects of stem cell factor (SCF) and flt3 ligand (FL) on the ex vivo expansion of human umbilical cord blood (CB)-derived CD34+ cells in combination with various cytokines, including interleukin (IL)-3, IL-6, IL-11, and c-Mpl ligand (thrombopoietin, TPO), in a short-term serum-free liquid suspension culture system. Among the two-factor combinations tested, SCF plus IL-3 most effectively expanded committed progenitor cells, including mixed colony-forming units (CFU-Mix). The expansion efficiency (EE) of FL for each progenitor was inferior to that of SCF in the presence of various cytokines, except TPO. IL-6 significantly increased the EE for granulocyte/macrophage colony-forming units (CFU-GM) obtained with SCF + IL-3 or FL + IL-3. Interestingly, TPO markedly augmented the EE for committed progenitors, including CFU-GM, erythroid burst-forming units (BFU-E), and CFU-Mix, in the presence of SCF + IL-3 or FL + IL-3. The combinations of SCF + IL-3 + TPO + IL-6 or IL-11 maximally stimulated the expansion of committed progenitors. The maximum EE for CFU-GM, BFU-E, and CFU-Mix was respectively 197-fold (day 14), 60-fold (day 7) and 51-fold (day 14). Other combinations of cytokines without IL-3 failed to expand effectively these committed progenitors. Our data demonstrate that it is possible to expand human CB-derived committed progenitors in vitro using SCF or FL with several other cytokines including TPO, and that IL-3 is the key cytokine promoting the expansion of human hematopoietic progenitors in the presence of SCF or FL.
authors.affiliation: Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohmizono
authors.forename: H
authors.initials: H
authors.lastname: Sakabe
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Tanimukai
authors.forename: T
authors.initials: T
authors.lastname: Matsumura
authors.forename: H
authors.initials: H
authors.lastname: Miyazaki
authors.forename: S D
authors.initials: SD
authors.lastname: Lyman
authors.forename: Y
authors.initials: Y
authors.lastname: Sonoda
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D005312:Fetal Blood; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology*; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D018952:Antigens, CD34; D017370:Interleukin-11; D007377:Interleukin-3; D015850:Interleukin-6; D008565:Membrane Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D013926:Thrombopoietin