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造血干细胞在成人骨髓干细胞龛中的定位。

Hematopoietic stem cell lodgment in the adult bone marrow stem cell niche.

机构信息

Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

出版信息

Int J Lab Hematol. 2010 Dec;32(6 Pt 2):551-8. doi: 10.1111/j.1751-553X.2010.01250.x.

Abstract

Treatment of malignant blood disorders, such as leukemia, that can provide a better chance of long-term remission involves myeloablation followed by transplantation of matched donor hematopoietic stem cells (HSCs). For successful engraftment and re-establishment of hematopoiesis to occur in the recipient, the transplanted HSCs must first migrate from the blood circulation to the bone marrow (BM), a process known as homing, then localize and anchor in suitable microenvironments within the BM, a process known as lodgment. After lodgment, the specific fate of the transplanted HSCs is determined through complex, bidirectional interactions with various stromal cell components in the niche. Ultimately, these interactions dictate the clinical outcome of the transplantation. Through the use of transgenic mouse models, considerable evidence has been accumulated in an attempt to unveil the possible underlying mechanisms that govern these processes. Here, we will emphasize the major factors that are involved in the regulation of lodgment of transplanted HSCs. Specifically, we will first introduce early observations on the spatial distribution of hematopoietic progenitors within the BM, then we will discuss the soluble factors, chemokines, cell-cell interactions, and cell-matrix interactions that have been studied and known to influence the site of HSC lodgment within the BM following transplantation.

摘要

治疗恶性血液病,如白血病,可以提供更好的长期缓解机会,包括骨髓清除后移植匹配供体造血干细胞(HSCs)。为了使移植的 HSCs 在受体内成功植入和重建造血,它们必须首先从血液循环迁移到骨髓(BM),这一过程称为归巢,然后在 BM 内的合适微环境中定位和锚定,这一过程称为定殖。定殖后,通过与龛内各种基质细胞成分的复杂双向相互作用,决定了移植 HSCs 的特定命运。最终,这些相互作用决定了移植的临床结果。通过使用转基因小鼠模型,已经积累了大量证据,试图揭示控制这些过程的潜在机制。在这里,我们将重点介绍调节移植 HSCs 定殖的主要因素。具体来说,我们将首先介绍造血祖细胞在 BM 内空间分布的早期观察结果,然后讨论已研究并已知影响移植后 HSC 在 BM 内定殖部位的可溶性因子、趋化因子、细胞-细胞相互作用和细胞-基质相互作用。

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