title: Systematic investigation of oxygen and growth factors in clinically valid ex vivo expansion of cord blood CD34(+) hematopoietic progenitor cells.
abstract: OBJECTIVE
  Cord blood is considered to be a superior source of hematopoietic stem and progenitor cells for transplantation, but clinical use is limited primarily because of the low numbers of cells harvested. Ex vivo expansion has the potential to provide a safe, effective means of increasing cell numbers. However, an absence of consensus regarding optimum expansion conditions prevents standard implementation. Many studies lack clinical applicability, or have failed to investigate the combinational effects of different parameters.
  
  
  METHODS
  This is the first study to characterize systematically the effect of growth factor combinations across multiple oxygen levels on the ex vivo expansion of cord blood CD34(+) hematopoietic cells utilizing clinically approvable reagents and methodologies throughout.
  
  
  RESULTS
  Optimal fold expansion, as assessed both phenotypically and functionally, was greatest with thrombopoietin, stem cell factor, Flt-3 ligand and interleukin-6 at an oxygen level of 10%. With these conditions, serial expansion showed continual target population expansion and consistently higher expression levels of self-renewal associated genes.
  
  
  CONCLUSIONS
  This study has identified optimized fold expansion conditions, with the potential for direct clinical translation to increase transplantable cell dose and as a baseline methodology against which future factors can be tested.
authors.affiliation: Barwon Biomedical Research, Barwon Health, Geelong, Australia. melinda.tursky@hotmail.com
authors.forename: Melinda L
authors.initials: ML
authors.lastname: Tursky
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Collier
authors.forename: Alister C
authors.initials: AC
authors.lastname: Ward
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kirkland
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005312:Fetal Blood / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051917:Leukosialin / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010641:Phenotype; D015203:Reproducibility of Results
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D051917:Leukosialin; D010100:Oxygen