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成人骨髓和脐带血中原始贴壁祖细胞的祖细胞更新概率(PPR)及克隆形成子代(CFU-GM)的产生

Probability of progenitor renewal (PPR) and production of clonogenic progeny (CFU-GM) by primitive adherent progenitor cells in adult human bone marrow and umbilical cord blood.

作者信息

Gordon M Y, Lewis J L, Scott M A, Roberts I A, Goldman J M

机构信息

Leukaemia Research Fund Centre for Adult Leukaemia, Royal Postgraduate Medical School, London.

出版信息

Br J Haematol. 1995 Aug;90(4):744-9. doi: 10.1111/j.1365-2141.1995.tb05191.x.

DOI:10.1111/j.1365-2141.1995.tb05191.x
PMID:7669652
Abstract

Human haemopoietic tissues contain primitive plastic-adherent progenitor cells (P delta cells) that can be detected by measurement of their granulocyte-macrophage colony-forming cell (CFU-GM) progeny. Limiting dilution analysis and Poisson statistics are necessary for determining the frequency of P delta cells because each of them produces several CFU-GM. Limiting dilution also permits measurement of the abilities of individual P delta progenitors to produce CFU-GM. Here we report that the frequencies of P delta progenitors in cord blood and adult marrow are similar (5.6 and 7.8/10(5) mononuclear cells respectively) and individual cord blood P delta progenitors produce fewer CFU-GM than adult P delta progenitors. To test the possibility that the lower production of differentiated progeny by cord blood cells was the result of a higher rate of self-renewal, we devised a two-stage limiting dilution assay relying on the relative production of CFU-GM after two consecutive weeks of incubation. The probability of progenitor renewal (PPR) was derived from the number of wells (progenitors) that produced CFU-GM on both occasions compared with the number that produced CFU-GM on the first occasion only. The total number of CFU-GM produced on the second occasion compared with the number produced on the first occasion provided an index of the overall change in the size of the P delta cell population. The data indicate that P delta cells in cord blood have a higher PPR (0.59) than those in adult marrow (0.36). Also, the relative numbers of CFU-GM produced in the second and first weeks were greater for cord blood (1.2) than for adult marrow (0.36). Therefore P delta cells in cord blood have a greater capacity for self-maintenance and possibly for expansion than P delta cells in adult marrow.

摘要

人类造血组织含有原始的塑料黏附祖细胞(Pδ细胞),可通过测量其粒细胞-巨噬细胞集落形成细胞(CFU-GM)后代来检测。由于每个Pδ细胞都会产生多个CFU-GM,因此需要进行有限稀释分析和泊松统计来确定Pδ细胞的频率。有限稀释还允许测量单个Pδ祖细胞产生CFU-GM的能力。我们在此报告,脐带血和成人骨髓中Pδ祖细胞的频率相似(分别为5.6和7.8/10⁵个单核细胞),且单个脐带血Pδ祖细胞产生的CFU-GM比成人Pδ祖细胞少。为了测试脐带血细胞分化后代产量较低是否是自我更新率较高的结果,我们设计了一种两阶段有限稀释试验,该试验依赖于连续两周孵育后CFU-GM的相对产量。祖细胞更新概率(PPR)源自两次都产生CFU-GM的孔(祖细胞)数量与仅在第一次产生CFU-GM的孔数量之比。第二次产生的CFU-GM总数与第一次产生的CFU-GM总数相比,提供了Pδ细胞群体大小总体变化的指标。数据表明,脐带血中的Pδ细胞比成人骨髓中的Pδ细胞具有更高的PPR(0.59)。此外,脐带血在第二周和第一周产生的CFU-GM相对数量(1.2)大于成人骨髓(0.36)。因此,脐带血中的Pδ细胞比成人骨髓中的Pδ细胞具有更大的自我维持能力,可能也具有更大的扩增能力。

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