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

Talkhoncheh, Mehrnaz Safaee LU ; Subramaniam, Agatheeswaran LU ; Magnusson, Mattias LU ; Kumar, Praveen; Larsson, Jonas LU and Baudet, Aurélie LU (2018) In Haematologica 103(9). p.1444-1450
Abstract

Despite extensive studies, defining culture conditions in which hematopoietic stem cells can be expanded ex vivo 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 ex vivo 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... (More)

Despite extensive studies, defining culture conditions in which hematopoietic stem cells can be expanded ex vivo 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 ex vivo 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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Haematologica
volume
103
issue
9
pages
7 pages
publisher
Ferrata Storti Foundation
external identifiers
  • scopus:85052894770
ISSN
0390-6078
DOI
10.3324/haematol.2018.188466
language
English
LU publication?
yes
id
c7295865-5829-4a4f-9837-8d4747f60b6d
date added to LUP
2018-10-16 14:59:16
date last changed
2019-03-26 17:12:41
@article{c7295865-5829-4a4f-9837-8d4747f60b6d,
  abstract     = {<p>Despite extensive studies, defining culture conditions in which hematopoietic stem cells can be expanded ex vivo 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 ex vivo 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.</p>},
  author       = {Talkhoncheh, Mehrnaz Safaee and Subramaniam, Agatheeswaran and Magnusson, Mattias and Kumar, Praveen and Larsson, Jonas and Baudet, Aurélie},
  issn         = {0390-6078},
  language     = {eng},
  number       = {9},
  pages        = {1444--1450},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {Transient inhibition of NF-κB signaling enhances ex vivo propagation of human hematopoietic stem cells},
  url          = {http://dx.doi.org/10.3324/haematol.2018.188466},
  volume       = {103},
  year         = {2018},
}