The expansion of murine bone marrow cells preincubated in hypoxia as an in vitro indicator of their marrow-repopulating ability

被引:50
作者
Cipolleschi, MG
Rovida, E
Ivanovic, Z
Praloran, V
Olivotto, M
Dello Sbarba, P
机构
[1] Univ Florence, Dipartimento Patol & Oncol Sperimentali, I-50134 Florence, Italy
[2] Univ Limoges, Lab Hematol Expt, Limoges, France
关键词
hypoxia; culture-repopulating cells; marrow-repopulating ability; 5-fluorouracil; hypoxic culture repopulating ability (HCRA);
D O I
10.1038/sj.leu.2401744
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In liquid cultures of murine bone marrow cells stimulated with interleukin-3 and granulocyte/macrophage colony-stimulating factor, hypoxia (1% oxygen) induced a reversible block of hematopoiesis, maintaining the progenitors' expansion potential unreduced. Progenitors repopulating day-14 hypoxic cultures with cells or granulocyte/macrophage colony-forming units (CFU-GM) were found, on the basis of their maintenance in hypoxia (12% and 76%, respectively), to belong to different subsets, the latter being much more efficiently maintained. The maintenance in hypoxic cultures of progenitors detectable by marrow-repopulating ability (MRA) assay was 18% for MRA(cell) progenitors and 69% for MRA(CFU) progenitors. Thus, the repopulation of hypoxic cultures with cells or CFU-GM closely reflected the presence of progenitors capable of repopulating, with cells or CFU-GM, the bone marrow of lethally irradiated syngeneic animals. Progenitors repopulating hypoxic cultures were, like MRA progenitors, significantly resistant to 5-fluorouracil, progenitors repopulating cultures with CFU-GM being two-fold more resistant than those repopulating cultures with cells. We concluded that the repopulation of day-14 hypoxic cultures occurring after their transfer to air is to be considered an indicator of the maintenance of MRA progenitors in hypoxia. The relevance of these results to stem cell biology and their potential practical applications are discussed.
引用
收藏
页码:735 / 739
页数:5
相关论文
共 16 条
[1]  
CIPOLLESCHI MG, 1993, BLOOD, V82, P2031
[2]  
Cipolleschi MG, 1997, EXP HEMATOL, V25, P1187
[3]  
DELLOSBARBA P, 1987, EXP HEMATOL, V15, P137
[4]  
HODGSON GS, 1984, EXP HEMATOL, V12, P683
[5]   Orderly process of sequential cytokine stimulation is required for activation and maximal proliferation of primitive human bone marrow CD34(+) hematopoietic progenitor cells residing in G(0) [J].
Ladd, AC ;
Pyatt, R ;
Gothot, A ;
Rice, S ;
McMahel, J ;
Traycoff, CM ;
Srour, EF .
BLOOD, 1997, 90 (02) :658-668
[6]   GROWTH-FACTOR REQUIREMENTS FOR SURVIVAL IN G0 AND ENTRY INTO THE CELL-CYCLE OF PRIMITIVE HUMAN HEMATOPOIETIC PROGENITORS [J].
LEARY, AG ;
ZENG, HQ ;
CLARK, SC ;
OGAWA, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) :4013-4017
[7]  
LORD BI, 1975, BLOOD, V46, P65
[8]  
LORD BI, 1992, CONCISE REV CLIN EXP, P225
[9]   THE DEVELOPMENT OF SPATIAL DISTRIBUTIONS OF CFU-S AND INVITRO CFC IN FEMORA OF MICE OF DIFFERENT AGES [J].
MASON, TM ;
LORD, BI ;
HENDRY, JH .
BRITISH JOURNAL OF HAEMATOLOGY, 1989, 73 (04) :455-461