Functional analysis of initial cell divisions defines the subsequent fate of individual human CD34+CD38- cells

被引:35
作者
Punzel, M [1 ]
Zhang, T [1 ]
Liu, DH [1 ]
Eckstein, V [1 ]
Ho, AD [1 ]
机构
[1] Heidelberg Univ, Dept Med 5, D-69115 Heidelberg, Germany
关键词
D O I
10.1016/S0301-472X(02)00781-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. We assessed the relationship of individual cell divisional behavior with the functional fate of stem cell candidates at the single cell level. Materials and Methods. Individual CD34(+)CD38(-) cells derived from cord blood (88-352 cells in each of 25 experiments) were cultured in early-acting conditioned medium (EACM) or late-acting proliferation medium (LAPM). The initial cell divisions were microscopically monitored every 12 to 24 hours and then assessed for primitive function in the myeloid lymphoid-initiating cell assay and committed function in the colony-forming cell (CFC) assay. Results. Despite a higher proliferative capacity in LAPM. significantly more quiescent cells (11.1 +/- 1.7%) were found in LAPM than in EACM cultures (1.1 +/- 0.4%;p < 0.001). No differences were observed in the initially plated CD34(-)Cd38(-) cells that produced asymmetrically dividing progeny. The majority of cells with subsequent ML-IC function divided in EACM but were found among quiescent cells in LAPM conditions. All cycling cells with subsequent ML-IC capacity initially remained quiescent for at least 96 hours. All ML-IC had been recruited exclusively (100%) from either cytokine nonresponsive (quiescent) or slow and asymmetrically dividing cells (1-2 divisions). In contrast, the majority of CFCs entered the cell cycle immediately after plating, have divided more than two times, and only 20.2 +/- 5.5% of the cycled CFC divided asymmetrically. Conclusions. Asymmetric divisional behavior of CD34(+)CD38(-) cells cannot be influenced by culture conditions. Primitive ML-IC can be distinguished from committed CFC by, initial quiescence or asymmetric divisions. Committed CFC cycle rapidly and symmetrically. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.
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页码:464 / 472
页数:9
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