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经骨髓内注射研究人脐血源 CD34(-)SCID 重建细胞的体内动力学。

In vivo dynamics of human cord blood-derived CD34(-) SCID-repopulating cells using intra-bone marrow injection.

机构信息

Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8506, Japan.

出版信息

Leukemia. 2010 Jan;24(1):162-8. doi: 10.1038/leu.2009.206. Epub 2009 Oct 1.

DOI:10.1038/leu.2009.206
PMID:19798093
Abstract

The identification of human CD34-negative (CD34(-)) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. This study investigated the long-term repopulating capacity and redistribution kinetics of human cord blood-derived CD34(-) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) and compared them with those of CD34(+)CD38(+) and CD34(+)CD38(-) SRCs using the intra-bone marrow injection (IBMI) to clarify the characteristics of CD34(-) SRCs. On the basis of the limiting dilution analyses data, estimated numbers of CD34(+)CD38(+), CD34(+)CD38(-), and CD34(-) SRCs were transplanted to NOD/SCID mice by IBMI. The human cell repopulation at the site of injection and the other bones were serially investigated. Interestingly, CD34(+)CD38(+), CD34(+)CD38(-), and CD34(-) SRCs began to migrate to other bones 2 and 5 weeks after the transplantation, respectively. Accordingly, the initiation of migration seemed to differ between the CD34(+) and CD34(-) SRCs. In addition, CD34(+)CD38(+) SRCs only sustained a short-term repopulation. However, both CD34(+)CD38(-) and CD34(-) SRCs had longer-term repopulation capacity. Taken together, these findings showed that CD34(-) SRCs show different in vivo kinetics, thus suggesting that the identified CD34(-) SRCs are a distinct class of primitive HSCs in comparison to the CD34(+)CD38(+) and CD34(+)CD38(-) SRCs.

摘要

人 CD34 阴性(CD34(-))造血干细胞(HSCs)的鉴定为人类 HSC 区室中的层次结构提供了新概念。本研究通过骨髓内注射(IBMI)调查了人脐血来源的 CD34(-)严重联合免疫缺陷(SCID)-重建造血细胞(SRC)的长期重建造血能力和再分布动力学,并将其与 CD34(+)CD38(+)和 CD34(+)CD38(-)SRC 进行比较,以阐明 CD34(-)SRC 的特征。基于限制稀释分析数据,通过 IBMI 将估计数量的 CD34(+)CD38(+)、CD34(+)CD38(-)和 CD34(-)SRC 移植到 NOD/SCID 小鼠中。连续研究了注射部位和其他骨骼中人细胞的再群体。有趣的是,CD34(+)CD38(+)、CD34(+)CD38(-)和 CD34(-)SRC 分别在移植后 2 周和 5 周开始迁移到其他骨骼。因此,CD34(+)和 CD34(-)SRC 之间的迁移似乎存在差异。此外,CD34(+)CD38(+)SRC 仅维持短期重建造血。然而,CD34(+)CD38(-)和 CD34(-)SRC 均具有更长的重建造血能力。总之,这些发现表明 CD34(-)SRC 显示出不同的体内动力学,因此表明与 CD34(+)CD38(+)和 CD34(+)CD38(-)SRC 相比,鉴定的 CD34(-)SRC 是一种不同的原始 HSC 类。

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