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Haematologica 2018 Volume 103(10):1604-1615
1Etablissement Français du Sang Nouvelle Aquitaine, Bordeaux, France; 2U1035 INSERM/Bordeaux University, France; 3Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Ferrata Storti Foundation
Hematopoiesis
Repopulating hematopoietic stem cells from steady-state blood before and after ex vivo culture are enriched in the CD34+CD133+CXCR4low fraction
Véronique Lapostolle,1,2 Jean Chevaleyre,1,2 Pascale Duchez,1,2 Laura Rodriguez,1,2 Marija Vlaski-Lafarge,1,2 Ioanna Sandvig,3 Philippe Brunet de la Grange1,2 and Zoran Ivanovic1,2
ABSTRACT
The feasibility of ex vivo expansion allows us to consider the steady- state peripheral blood as an alternative source of hematopoietic stem progenitor cells for transplantation when growth factor- induced cell mobilization is contraindicated or inapplicable. Ex vivo expansion dramatically enhances the in vivo reconstituting cell population from steady-state blood. In order to investigate phenotype and the expression of homing molecules, the expression of CD34, CD133, CD90, CD45RA, CD26 and CD9 was determined on sorted CD34+ cells accord- ing to CXCR4 (“neg“, “low” “bright”) and CD133 expression before and after ex vivo expansion. Hematopoietic stem cell activity was determined in vivo on the basis of hematopoietic repopulation of primary and second- ary recipients - NSG immuno-deficient mice. In vivo reconstituting cells in the steady-state blood CD34+ cell fraction before expansion belong to the CD133+ population and are CXCR4low or, to a lesser extent, CXCR4neg, while after ex vivo expansion they are contained only in the CD133+CXCR4low cells. The failure of the CXCR4bright population to engraft is probably due to the exclusive expression of CD26 by these cells. The limiting-dilution analysis showed that both repopulating cell number and individual proliferative capacity were enhanced by ex vivo expansion. Thus, steady-state peripheral blood cells exhibit a different phenotype compared to mobilized and cord blood cells, as well as to those issued from the bone marrow. These data represent the first phe- notypic characterization of steady-state blood cells exhibiting short- and long-term hematopoietic reconstituting potential, which can be expand- ed ex vivo, a sine qua non for their subsequent use for transplantation.
Introduction
The introduction into clinical practice of “mobilization” from the bone marrow to peripheral blood, was an approach that resulted in an impressive increase of the number of hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) available for collection by cytapheresis. As such, this approach represented a revolutionary event in hematopoietic transplantation1 and, as a result, strategies involving steady-state peripheral blood (SS-PB)2 were abandoned. However, the pro- cedure of mobilization of HPCs and HSCs, as well as their collection from the bone marrow, are not without risks.3 Such risks can also effectively pose a deterrent to the recruitment of voluntary donors. Besides, mobilization is contraindicated in some cases, leading to the exclusion of the potential donors. Thus, avoiding mobilization
Correspondence:
zoran.ivanovic@efs.sante.fr
Received: November 3, 2017. Accepted: May 24, 2018. Pre-published: June 1, 2018.
doi:10.3324/haematol.2017.183962
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/10/1604
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