人类胎儿发育过程中CD34+、CD38-骨髓祖细胞生长特性的变化。

Changes in the growth properties of CD34+, CD38- bone marrow progenitors during human fetal development.

作者信息

Waller E K, Huang S, Terstappen L

机构信息

Emory University, Division of Hematology/Oncology, Atlanta, GA 30322, USA.

出版信息

Blood. 1995 Jul 15;86(2):710-8.

PMID:7541673

Abstract

We have previously described the isolation of separate populations of CD34+, CD38- stromal and hematopoietic progenitors cells within fetal bone marrow. The CD34+, CD38-, CD50+, HLA-DR+ population contained the majority of primitive hematopoietic progenitor cells, whereas stromal progenitors were contained within the CD34+, CD38-, CD50-, HLA-DR- population. In this study, we compared the frequencies and total numbers of clonogenic CD34+, CD38- stromal and hematopoietic cells as a function of fetal gestational age using single-cell fluorescent-activated cell sorting (FACS). At 14 weeks of gestation, 1/500 fetal bone marrow mononuclear cells were primitive hematopoietic CD34+, CD38-, HLA-DR+ progenitor cells, whereas 1/1,000 were stromal progenitors with the CD34+, CD38-, HLA-DR- phenotype. During fetal ontogeny there was a continuous, age-dependent decrease in the frequency of stromal progenitors, such that, at 24 weeks of gestation, only 1/100,000 of bone marrow cells had the CD34+, CD38-, HLA-DR- phenotype and were clonogenic stromal cells when isolated by FACS. In contrast, 1/250 bone marrow cells in a 24-week fetus had the CD34+, CD38-, HLA-DR+ phenotype and were clonogenic hematopoietic progenitors. The decrease in the frequency of stromal progenitors was a function of both a decreased frequency of cells with the CD34+, CD38-, HLA-DR- phenotype and a decrease in the growth potential of individual with this phenotype. The total numbers of mononuclear cells and the total numbers of hematopoietic progenitors in two fetal femurs increased in parallel, 100-fold, between 14 and 24 weeks of gestation. In contrast, the total numbers of clonogenic CD34+, CD38-, HLA-DR- stromal progenitor cells remained constant during this period. Although adult bone marrow samples contained stromal progenitor cells at a frequency of approximately 1/7,000 mononuclear cells, clonogenic stromal cells with the CD34+, CD38-, HLA-DR- phenotype could not be isolated by single-cell FACS from these samples. Thus, there are significant differences between the frequencies and biologic characteristics of stromal and hematopoietic stem cells during fetal and postnatal ontogeny.

摘要

我们之前曾描述过从胎儿骨髓中分离出不同群体的CD34⁺、CD38⁻基质祖细胞和造血祖细胞。CD34⁺、CD38⁻、CD50⁺、HLA-DR⁺群体包含了大多数原始造血祖细胞，而基质祖细胞则存在于CD34⁺、CD38⁻、CD50⁻、HLA-DR⁻群体中。在本研究中，我们使用单细胞荧光激活细胞分选（FACS）技术，比较了作为胎儿胎龄函数的克隆形成性CD34⁺、CD38⁻基质细胞和造血细胞的频率及总数。在妊娠14周时，1/500的胎儿骨髓单个核细胞是原始造血性CD34⁺、CD38⁻、HLA-DR⁺祖细胞，而1/1000是具有CD34⁺、CD38⁻、HLA-DR⁻表型的基质祖细胞。在胎儿发育过程中，基质祖细胞的频率持续且随年龄下降，以至于在妊娠24周时，通过FACS分离时，只有1/100,000的骨髓细胞具有CD34⁺、CD38⁻、HLA-DR⁻表型且是克隆形成性基质细胞。相比之下，24周胎儿中1/250的骨髓细胞具有CD34⁺、CD38⁻、HLA-DR⁺表型且是克隆形成性造血祖细胞。基质祖细胞频率的下降是具有CD34⁺、CD38⁻、HLA-DR⁻表型的细胞频率降低以及该表型个体生长潜能下降共同作用的结果。在妊娠14至24周期间，两根胎儿股骨中的单个核细胞总数和造血祖细胞总数平行增加了100倍。相比之下，在此期间，克隆形成性CD34⁺、CD38⁻、HLA-DR⁻基质祖细胞的总数保持不变。尽管成人骨髓样本中基质祖细胞的频率约为1/7000单个核细胞，但通过单细胞FACS无法从这些样本中分离出具有CD34⁺、CD38⁻、HLA-DR⁻表型的克隆形成性基质细胞。因此，在胎儿期和出生后发育过程中，基质干细胞和造血干细胞在频率和生物学特性上存在显著差异。