Transient inhibition of NF-κB signaling enhances ex vivo propagation of human hematopoietic stem cells

Despite extensive studies, defining culture conditions in which hematopoietic stem cells can be expanded has been challenging. Here we show that chemical inhibition of the NF-κB signaling pathway leads to a significant improvement of hematopoietic stem cell function from cultured human umbilical cor...

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Bibliographic Details
Published inHaematologica (Roma) Vol. 103; no. 9; pp. 1444 - 1450
Main Authors Talkhoncheh, Mehrnaz Safaee, Subramaniam, Agatheeswaran, Magnusson, Mattias, Kumar, Praveen, Larsson, Jonas, Baudet, Aurélie
Format Journal Article
LanguageEnglish
Published Italy Ferrata Storti Foundation 01.09.2018
Subjects
Animals
Antigens, CD34 - metabolism
Basic Medicine
Biomarkers
Cell and Molecular Biology
Cell Culture Techniques
Cell Proliferation
Cell- och molekylärbiologi
Cells, Cultured
Clinical Medicine
Cytokines - metabolism
Hematologi
Hematology
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - metabolism
Humans
Immunophenotyping
Inflammation Mediators - metabolism
Klinisk medicin
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Mice
NF-kappa B - metabolism
Phenotype
Signal Transduction - drug effects
Thy-1 Antigens - metabolism
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Summary:Despite extensive studies, defining culture conditions in which hematopoietic stem cells can be expanded has been challenging. Here we show that chemical inhibition of the NF-κB signaling pathway leads to a significant improvement of hematopoietic stem cell function from cultured human umbilical cord blood derived CD34 cells. We found a distinct peak of activation of the NF-κB pathway shortly after cells were put in culture, and consequently inhibition of the pathway was both necessary and sufficient during the first 24 hours of culture where it reduced the levels of several pro-inflammatory cytokines. Taken together, NF-κB pathway inhibition facilitates propagation of hematopoietic stem cells in culture and may complement other strategies for hematopoietic stem cell expansion by relieving stress signals that are induced as an immediate response to culture initiation.
Bibliography:ObjectType-Article-1
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ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2018.188466