T-cell potential of human adult and cord blood hemopoietic stem cells expanded with the use of aryl hydrocarbon receptor antagonists |
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| Authors: | Stephen M Carlin David D Ma John J Moore |
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| Institution: | 1. Blood, Stem Cells & Cancer Research, St Vincent''s Institute for Applied Medical Research, Sydney, Australia;2. Department of Haematology, St Vincent''s Hospital, Sydney, Australia;1. Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan;2. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;3. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;4. Basic Science, Nursing Department, Meiho Institute of Technology, Pingtung, Taiwan;5. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan;6. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan;7. Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;8. Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan;1. State Key Laboratory for Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China;2. Department of Radiation Oncology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;3. Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea;4. Department of Blood Transfusion, Changhai Hospital, Shanghai, China;1. Thoracic Surgery Department, Icahn School of Medicine at Mount Sinai, New York, NY;2. Population Health Science and Policy Department, Icahn School of Medicine at Mount Sinai, New York, NY;3. Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY;4. Radiology Department, Mount Sinai Health System, Icahn School of Medicine, New York, NY;5. Department of Statistics, Stanford University, Stanford, CA;6. General Thoracic Surgery Division, General Thoracic Surgery Department, New York University Langone Medical Center, New York University School of Medicine, New York, NY;1. Division of Physiology, Livestock Research Institute, Council of Agriculture, Executive Yuan, Tainan, Taiwan;2. Department of Medical Research, Buddhist Tzu-Chi University, Hualien, Taiwan;3. Institute of Medical Science, Buddhist Tzu-Chi University, Hualien, Taiwan;4. Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan;5. Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan;6. Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan;7. Institute of Biotechnology, Southern Taiwan University, Tainan, Taiwan;1. Department of Cardiovascular Sciences, University of Leicester, UK;2. Syngenta Ltd., Jealott''s Hill, UK;3. MRC Toxicology Unit, University of Leicester, Leicester, UK |
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| Abstract: | Background aimsExpansion 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.MethodsAdult 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.ResultsBoth 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.ConclusionsThis 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. |
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