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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2744-2752
HEMATOPOIESIS
Adhesion of synchronized human hematopoietic progenitor cells to
fibronectin and vascular cell adhesion molecule-1 fluctuates
reversibly during cell cycle transit in ex vivo culture
Sandra Huygen,
Olivier Giet,
Vincent Artisien,
Ivano Di Stefano,
Yves Beguin, and
André Gothot
From the Departments of Clinical Hematology and
Laboratory Hematology, University of Liège, Belgium; and the
National Fund for Scientific Research, Brussels, Belgium.
Ex vivo expansion of hematopoietic stem/progenitor cells may result
in defective engraftment. Human cord blood CD34+ progenitor
cells were synchronized and assayed for adhesion and migration onto
fibronectin (Fn) and vascular cell adhesion molecule-1 (VCAM-1) at
different stages of a first cell cycle executed ex vivo. During S phase
transit, adhesion to Fn was transiently increased while binding to
VCAM-1 was reversibly decreased, after which adhesion to both ligands
returned to baseline levels with cell cycle completion. Transmigration
across Fn and VCAM-1 decreased irreversibly during S phase progression.
The function of  4 and 5 integrins was assessed with specific
neutralizing antibodies. In uncultured CD34+ cells and
long-term culture-initiating cells (LTC-ICs), both adhesion and
migration on Fn were inhibited by anti-4 but not by anti-5
antibodies. In mitotically activated CD34+ cells and
LTC-ICs, adhesion and migration on Fn were mainly dependent on 5
integrin and to a lesser extent on 4 integrin. Changes in integrin
function were not dependent on parallel modulation of integrin
expression. In conclusion, Fn and VCAM-1 binding of progenitor cells
fluctuates reversibly during cell cycle transit ex vivo. In addition,
our data show that mitogenic activation induces a shift from a dominant
4 to a preferential 5 integrin-dependent interaction with Fn.
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