title: T-cell potential of human adult and cord blood hemopoietic stem cells expanded with the use of aryl hydrocarbon receptor antagonists.
abstract: OBJECTIVE
  Expansion of hemopoietic stem cells (HSCs) in vitro is a potential strategy for improving transplant outcomes, but expansion methods tend to promote differentiation and loss of stem cell potential. Aryl hydrocarbon receptor antagonists (AhRAs) have recently been shown to protect HSC stemness during expansion; however, little is known of the T-cell regenerative capacity of AhRA-expanded HSCs. In this study, we confirm the protective effect of two commercially available AhRA compounds on HSCs from both cord blood (CB) and adult samples and assess the T-lymphocyte potential of the expanded cells.
  
  
  METHODS
  Adult mobilized peripheral blood and CB samples were purified to CD34(+) cells, which were expanded in vitro with cytokines and AhRAs. After 14 d, CD34(+) cells were re-isolated and then grown on in OP9Delta co-culture under conditions that allow T-lymphocyte differentiation. Cells were monitored weekly for T-lineage markers by flow cytometry.
  
  
  RESULTS
  Both AhRA compounds promoted maintenance of CD34 expression during 2 weeks of proliferation with growth factors, although adult cells proliferated markedly less than CB cells. AhRA-expanded CD34(+) cells from CB differentiated to T cells on OP9Delta co-culture with the same rate and time course as untreated cells. Adult cells, by contrast, had reduced differentiation to T cells, with donor-dependent variable responses.
  
  
  CONCLUSIONS
  This study shows that whereas AhRA treatment is effective in CB samples, expansion of adult HSCs is less successful and reflects their inherent poor potential in T-cell generation.
authors: Blood, Stem Cells & Cancer Research, St Vincent's Institute for Applied Medical Research, Sydney, Australia.
authors: Stephen M
authors: SM
authors: Carlin
authors: David D
authors: DD
authors: Ma
authors: John J
authors: JJ
authors: Moore
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D001391:Azo Compounds / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D011720:Pyrazoles / Q000008:administration & dosage*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
chemical_list: C511621:2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide; D018952:Antigens, CD34; D001391:Azo Compounds; D011720:Pyrazoles; D018336:Receptors, Aryl Hydrocarbon