Haematologica. 2018 Jun 7. pii: haematol.2018.188466. doi: 10.3324/haematol.2018.188466. [Epub ahead of print]

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

Safaee Talkhoncheh M¹, Subramaniam A¹, Magnusson M¹, Kumar P¹, Larsson J², Baudet A¹.

Abstract

Despite extensive studies, it has been challenging to define culture conditions in which hematopoietic stem cells (HSCs) can be expanded ex vivo. Here, we show that chemical inhibition of the NF-κB signaling pathway leads to a significant improvement of HSC 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 HSCs in culture and may complement other strategies for HSC expansion by relieving stress signals that are induced as an immediate response to culture initiation.