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First published online August 25, 2005
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2004-0351v1
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Submitted on December 10, 2004
Accepted on June 23, 2005

Original Article

Very low O2 concentration (0.1%) favors G0 return of dividing CD34+ cells

Francis Hermitte 1, Philippe Brunet de la Grange 2, Francis Belloc 3, Vincent Praloran 2*, Zoran Ivanovic 4

1 UMR 5164, Univerité de Bordeaux 2, Bordeaux, France
2 CNRS UMR 5164, Université de Bordeaux 2, Bordeaux, France
3 CHU de Bordeaux, Bordeaux, France
4 Etablissement Français du Sang Aquitaine-Limousin, Bordeaux, France

* To whom correspondence should be addressed. E-mail: vincent.praloran{at}u-bordeaux2.fr.


  Abstract

Physiological bone marrow oxygen concentrations are everywhere lower than 4% and almost null in some areas. We compared the effects of 20%, 3% and 0.1% O2 concentrations on cord blood CD34+ cell survival, cycle and functionality in serum free cultures for 72 h with or without interleukin-3 (IL-3). As from 24 h, IL-3 improved cell survival and proliferation in all conditions. After 72 h, cells were 1.5 and 2.5 times more in quiescence (G0) at 3% and 0.1% O2 respectively than at 20%; transforming growth factor-{beta} (TGF-{beta}) signaling seemed not to be involved. To explore cell cycle further, fresh CD34+ cells were stained with PKH26, cultured for 72 h, then undivided and divided cells were sorted. At 0.1% O2, 46.5 ± 19.1% of divided cells returned to G0 compared to 7.9% ± 0.3 at 20%. Colony formation and nonobese diabetic/severe combined immunodeficient mice engraftment efficiency were similar after 3 days at 20% and 0.1% O2 concentrations but lower than at T0. In conclusion, a low O2 concentration, close to those found in bone marrow stem cell niches, induces the G0 return of CD34+ cells without impairing their functional capacity.

Key Words. CD34, cell cycle, hematopoietic stem cell, hypoxia, oxygen




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