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T-cell potential of human adult and cord blood hemopoietic stem cells expanded with the use of aryl hydrocarbon receptor antagonists.
MedLine Citation:
PMID:  23321333     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND AIMS: 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:
Stephen M Carlin; David D Ma; John J Moore
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cytotherapy     Volume:  15     ISSN:  1477-2566     ISO Abbreviation:  Cytotherapy     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100895309     Medline TA:  Cytotherapy     Country:  England    
Other Details:
Languages:  eng     Pagination:  224-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 International Society for Cellular Therapy. All rights reserved.
Affiliation:
Blood, Stem Cells & Cancer Research, St Vincent's Institute for Applied Medical Research, Sydney, Australia.
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