Simultaneous maintenance of human cord blood SCID-repopulating cells and expansion of committed progenitors at low O2 concentration (3%).
In the present work, we tested the hypothesis that liquid cultures (LCs) of cord blood CD34+ cells at an appropriate low O2 concentration could simultaneously allow colony-forming cell (CFC) expansion and nonobese diabetic/severe combined immunodeficiency mice-repopulating cell (SRC) maintenance. We first found that 3% was the minimal O2 concentration, still allowing the same rate of CFC expansion as at 20% O2. We report here that 7-day LCs of cord blood CD34+ cells at 3% O2 maintain SRC better than at 20% O2 and allow a similar amplification of CFCs (35- to 50-fold) without modifying the CD34+ cell proliferation. Their phenotypic profile (antigens: HLA-DR, CD117, CD33, CD13, CD11b, CD14, CD15, and CD38) was not modified, with exception of CD133, whose expression was lower at 3% O2. These results suggest that low O2 concentrations similar to those found in bone marrow participates in the regulation of hematopoiesis by favoring stem cell-renewing divisions. This expansion method that avoids stem cell exhaustion could be of paramount interest in hematopoietic transplantation by allowing the use of small-size grafts in adults.
Ivanovic
Zoran
Z
Laboratory for Studies on Hematopoiesis: Molecular and Functional Aspects, Bordeaux 2 University, France. zoran.ivanovic@efs.sante.fr
Hermitte
Francis
F
Brunet de la Grange
Philippe
P
Dazey
Bernard
B
Belloc
Francis
F
Lacombe
Francis
F
Vezon
Gérard
G
Praloran
Vincent
V
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D005312:Fetal Blood / Q000276:immunology* / Q000378:metabolism; D006410:Hematopoiesis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D016513:Mice, SCID; D010101:Oxygen Consumption / Q000276:immunology; D010641:Phenotype; D011247:Pregnancy
D018952:Antigens, CD34; D000954:Antigens, Surface