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Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.

Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.

Authors :
Bourdieu, Antonin
Avalon, Maryse
Lapostolle, Véronique
Ismail, Sadek
Mombled, Margaux
Debeissat, Christelle
Guérinet, Marianne
Duchez, Pascale
Chevaleyre, Jean
Vlaski-Lafarge, Marija
Villacreces, Arnaud
Praloran, Vincent
Ivanovic, Zoran
de la Grange, Philippe Brunet
Source :
Journal of Cellular Physiology. Jan2018, Vol. 233 Issue 1, p338-349. 12p.
Publication Year :
2018

Abstract

Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219541
Volume :
233
Issue :
1
Database :
Academic Search Index
Journal :
Journal of Cellular Physiology
Publication Type :
Academic Journal
Accession number :
125370353
Full Text :
https://doi.org/10.1002/jcp.25881