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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 756-768
Chemokine SDF-1 enhances circulating CD34+ cell
proliferation in synergy with cytokines: possible role in progenitor
survival
Jean-Jacques Lataillade,
Denis Clay,
Catherine Dupuy,
Sylvain Rigal,
Claude Jasmin,
Philippe Bourin, and
Marie-Caroline Le Bousse-Kerdilès
From the Laboratoire d'Immunologie Cellulaire, Centre de
Transfusion Sanguine des Armées Jean Julliard, Clamart Cedex,
France; Institut National de la Santé et de la Recherche
Médicale, Hôpital Paul Brousse, Villejuif, France;
Hôpital d'Instruction des Armées Percy, Clamart Cedex,
France.
The chemokine stromal cell-derived factor-1 (SDF-1), and its
receptor, CXCR-4, have been implicated in the homing and mobilization of human CD34+ cells. We show here that SDF-1 may also be
involved in hematopoiesis, promoting the proliferation of human
CD34+ cells purified from normal adult peripheral blood
(PB). CXCR-4 was expressed on PB CD34+ cells. The amount
of CXCR-4 on PB CD34+ cells was 10 times higher when
CD34+ cells were purified following overnight incubation.
CXCR-4 overexpression was correlated with a primitive PB
CD34+ cell subset defined by a
CD34high CD38lowCD71lowc-KitlowThy-1+
antigenic profile. The functional significance of CXCR-4 expression was
ascertained by assessing the promoting effect of SDF-1 on cell
cycle, proliferation, and colony formation. SDF-1 alone increased the
percentage of CD34+ cells in the S+G2/M
phases and sustained their survival. In synergy with cytokines, SDF-1
increased PB CD34+ and
CD34highCD38low cell expansion and colony
formation. SDF-1 also stimulated the growth of colonies derived from
primitive progenitors released from quiescence by anti-TGF-
treatment. Thus, our results shed new light on the potential role of
this chemokine in the stem cell engraftment process, which involves
migration, adhesion, and proliferation. Furthermore, both
adhesion-induced CXCR-4 overexpression and SDF-1 stimulating activity
may be of clinical relevance for improving cell therapy settings in
stem cell transplantation.
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A. Peled, O. Kollet, T. Ponomaryov, I. Petit, S. Franitza, V. Grabovsky, M. M. Slav, A. Nagler, O. Lider, R. Alon, et al.
The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34+ cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice
Blood,
June 1, 2000;
95(11):
3289 - 3296.
[Abstract]
[Full Text]
[PDF]
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