title: Platelet-derived growth factor promotes ex vivo expansion of CD34+ cells from human cord blood and enhances long-term culture-initiating cells, non-obese diabetic/severe combined immunodeficient repopulating cells and formation of adherent cells.
abstract: Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells. In this study, we investigated the effects and mechanism of PDGF on the ex vivo expansion of cord blood CD34+ cells. Our data demonstrated that among various cytokine combinations of thrombopoietin (TPO), interleukin 1 beta (IL-1beta), IL-3, IL-6 and Flt-3 ligand (Flt-3L), TPO + IL-6 + Flt-3L was most efficient in promoting the expansion of CD34+ cells, CD34+CD38- cells, mixed-lineage colony-forming units (CFU-GEMM) and long-term culture-initiating cells (LTC-IC) by 21.7 +/- 5.00-, 103 +/- 27.9-, 10.7 +/- 7.94- and 6.52 +/- 1.51-fold, respectively, after 12-14 d of culture. The addition of PDGF increased the yield of these early progenitors by 45.0%, 66.5%, 45.1% and 79.8% respectively. More significantly, PDGF enhanced the engraftment of human CD45+ cells and their myeloid subsets (CD33+, CD14+ cells) in non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) mice. The expression of PDGF receptor (PDGFR)-beta was not detectable in fresh CD34+ cells but was upregulated after culture for 3 d. PDGF also enhanced the development of adherent cells/clusters that expressed the endothelial markers VE-cadherin and CD31. These findings suggest that PDGF is an effective cytokine for the ex vivo expansion of early stem and progenitor cells. The mechanism could be mediated by PDGFR-beta on committed CD34+ progenitor cells and/or secondary to the stimulation of autologous, stromal feeder cells.
authors.affiliation: Department of Paediatrics, The Chinese University of Hong Kong, 6th Floor, Prince of Wales Hospital, Shatin, N.T., Hong Kong.
authors.forename: Rui Jun
authors.initials: RJ
authors.lastname: Su
authors.forename: Xiao Bing
authors.initials: XB
authors.lastname: Zhang
authors.forename: Karen
authors.initials: K
authors.lastname: Li
authors.forename: Mo
authors.initials: M
authors.lastname: Yang
authors.forename: Chi Kong
authors.initials: CK
authors.lastname: Li
authors.forename: Tai Fai
authors.initials: TF
authors.lastname: Fok
authors.forename: Anthony Edward
authors.initials: AE
authors.lastname: James
authors.forename: Henry
authors.initials: H
authors.lastname: Pong
authors.forename: Patrick Man Pan
authors.initials: PM
authors.lastname: Yuen
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000097:blood*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D005312:Fetal Blood / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D013234:Stem Cells
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor