title: Effect of PEG-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on growth and differentiation of the HEL cell line.
abstract: OBJECTIVE
  Thrombopoietin has been established as the major regulator of megakaryocyte and platelet production. In this study we evaluated the effects of PEG-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated and truncated form of thrombopoietin, on the growth and differentiation of the HEL cell line. As a model system we chose the pluripotent HEL line that acquires multiple markers of the megakaryocyte/platelet phenotype following treatment with phorbol esters, and, more importantly, expresses the receptor for thrombopoietin (Mpl receptor) at its cellular surface.
  
  
  METHODS
  The effect of PEG-rHuMGDF on HEL proliferation/differentiation was evaluated in a liquid culture assay.
  
  
  RESULTS
  Peg-rHuMGDF do not increase the proliferative capacity of HEL cell but, in parallel experiments, HEL cells showed a more mature and differentiated pattern after exposure to the cytokine. Our results show that PEG-rHuMGDF, at the optimal doses of 100-150 ng/mL, is able to induce: 1) morphological changes with the formation of cytoplasmic protrusions; 2) increased ploidy as demonstrated by cytofluorimetric analysis; 3) increased expression of megakaryocyte markers, including glycoprotein IIb-IIIa and the platelet-specific alloantigen (PIA1).
  
  
  CONCLUSIONS
  These findings show that HEL cells represent a useful model to investigate the differentiative properties of thrombopoietin in the megakaryocyte compartment.
authors.affiliation: Istituto di Ematologia e Oncologia Medica L. e A. Seràgnoli, University of Bologna, Italy. seragnol@kaiser.alma.unibo.it
authors.forename: L
authors.initials: L
authors.lastname: Catani
authors.forename: L
authors.initials: L
authors.lastname: Gugliotta
authors.forename: M
authors.initials: M
authors.lastname: Motta
authors.forename: P
authors.initials: P
authors.lastname: Tazzari
authors.forename: S
authors.initials: S
authors.lastname: Baravelli
authors.forename: S
authors.initials: S
authors.lastname: Tura
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin