Very low O2 concentration (0.1%) favors G0 return of dividing CD34+ cells.
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 hours with or without interleukin-3 (IL-3). As from 24 hours, IL-3 improved cell survival and proliferation in all conditions. After 72 hours, 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 signaling seemed not to be involved. To explore cell cycle further, fresh CD34+ cells were stained with PKH26 and cultured for 72 hours, and then undivided and divided cells were sorted. At 0.1% O2, 46.5%+/-19.1% of divided cells returned to G0 compared with 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.
Hermitte
Francis
F
CNRS UMR 5164, Université de Bordeaux 2, 33076 Bordeaux CEDEX, France.
Brunet de la Grange
Philippe
P
Belloc
Francis
F
Praloran
Vincent
V
Ivanovic
Zoran
Z
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002453:Cell Cycle; D002470:Cell Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D007377:Interleukin-3; D019089:Stem Cell Factor; D010100:Oxygen