title: Thrombopoietin alone or in the presence of stem cell factor supports the growth of KIT(CD117)low/ MPL(CD110)+ human mast cells from hematopoietic progenitor cells.
abstract: OBJECTIVE
  Thrombopoietin (TPO) is known to promote platelet number, have growth-promoting potential for human megakaryocytes (HuMKs), and increase erythrocyte, monocyte, mast cell, and granulocyte numbers in the presence of additional growth factors. We explored the ability of TPO alone or in the presence of stem cell factor (SCF) to support human mast cells (HuMCs).
  
  
  METHODS
  CD34+ pluripotent and CD34+/CD117+/CD13+ HuMC progenitor cells were cultured in rhTPO and examined for HuMCs. Similarly, we added rhTPO to CD34(+) cells cultured in stem cell factor (SCF), which promotes HuMC development.
  
  
  RESULTS
  When CD34+ cells were cultured in 10 ng/mL rhTPO and 10 ng/mL rhSCF, TPO enhanced HuMC numbers compared to rhSCF alone. Higher concentrations of rhTPO (50 ng/mL) in the presence of 100 ng/mL rhSCF inhibited the rhSCF-dependent subpopulation of CD117high HuMCs, while promoting CD117low HuMCs. Human CD34+/CD117+/CD13+ cells cultured in rhTPO alone for 1 to 2 weeks differentiated into CD41+/CD110+ HuMKs (85-90%) and FcepsilonRI+/CD117low/CD13+ HuMCs (5-10%). RhTPO-induced HuMCs expressed the TPO (CD110) receptor, tryptase, and chymase and survived when recultured in rhSCF.
  
  
  CONCLUSIONS
  The effect of TPO on HuMCs in the presence of rhSCF varies, depending on the relative concentration of each growth factor, while TPO alone or in combination with rhSCF supports a unique population of CD117low/CD110+ HuMCs.
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA. Akirshenba@niaid.nih.gov
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Kirshenbaum
authors.forename: Cem
authors.initials: C
authors.lastname: Akin
authors.forename: Julie P
authors.initials: JP
authors.lastname: Goff
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
mesh_terms: D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004347:Drug Interactions; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D008407:Mast Cells / Q000166:cytology*; D011518:Proto-Oncogene Proteins; D019009:Proto-Oncogene Proteins c-kit; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D019089:Stem Cell Factor / Q000494:pharmacology*; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D019089:Stem Cell Factor; C082218:MPL protein, human; D013926:Thrombopoietin; D019009:Proto-Oncogene Proteins c-kit