title: Thrombopoietin is synergistic with other cytokines for expansion of cord blood progenitor cells.
abstract: We investigated the effects of recombinant human thrombopoietin (TPO) in combination with various cytokines including erythropoietin (EPO), interleukin-3 (IL-3), interleukin-6 (IL-6), and stem cell factor (SCF) on megakaryopoiesis, and the expansion of CD34+CD41a+ cells from human cord blood CD34+ cells with these cytokines under serum-free conditions. Human cord blood CD34+ cells were cultured in Megacult (Stem Cell Technologies Inc. Vancouver, Canada) in the presence of recombinant growth factors. Colony-forming unit-megakaryocyte (CFU-M) colonies were counted on day 14. CD34+CD41a+ and CD34-CD41a+ cell expansion was analyzed using a serum-free liquid culture system for 7 days with recombinant growth factors. TPO alone had a concentration-dependent effect on megakaryocyte colony growth. At concentrations above 1 ng/ml, TPO supported significant CFU-Meg colony formation in a concentration-dependent manner. The combination of TPO plus other cytokines, including EPO, IL-3, and SCF, resulted in a synergistic enhancement of the number of CFU-Meg colonies, but IL-6 failed to enhance the effect of TPO. The number of CD41a+ cells increased after 7 days in liquid culture of human cord blood CD34+ cells with various cytokines (EPO, IL-3, IL-6, SCF) combined with TPO, but SCF plus TPO only resulted in a significant synergistic increment of CD34+CD41a+ cells compared with TPO alone. The results of the present study indicate that EPO, IL-3, and SCF can be synergistic with TPO to stimulate proliferation of CFU-Meg and suggest that SCF plus TPO can expand CD34+CD41a+ cells to effect the rapid recovery of platelets in patients following stem cell transplantation.
authors.affiliation: Department of Internal Medicine and Institute for Clinical Molecular Biology Research, Soon Chun Hyang University College of Medicine, Seoul, Korea. jhwon@hosp.sch.ac.kr
authors.forename: J H
authors.initials: JH
authors.lastname: Won
authors.forename: S D
authors.initials: SD
authors.lastname: Cho
authors.forename: S K
authors.initials: SK
authors.lastname: Park
authors.forename: G T
authors.initials: GT
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Baick
authors.forename: W S
authors.initials: WS
authors.lastname: Suh
authors.forename: D S
authors.initials: DS
authors.lastname: Hong
authors.forename: H S
authors.initials: HS
authors.lastname: Park
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000276:immunology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D016207:Cytokines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D013926:Thrombopoietin