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本文引用的文献

1
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.前列腺素调节的脐带血造血干细胞移植。
Blood. 2013 Oct 24;122(17):3074-81. doi: 10.1182/blood-2013-05-503177. Epub 2013 Aug 30.
2
Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment.定量成像技术在骨髓微环境中造血干细胞和祖细胞定位及缺氧状态的研究
Nat Cell Biol. 2013 May;15(5):533-43. doi: 10.1038/ncb2730. Epub 2013 Apr 28.
3
Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo.葡萄糖代谢影响体内造血干细胞诱导的时空发作和幅度。
Blood. 2013 Mar 28;121(13):2483-93. doi: 10.1182/blood-2012-12-471201. Epub 2013 Jan 22.
4
Pharmacologic stabilization of HIF-1α increases hematopoietic stem cell quiescence in vivo and accelerates blood recovery after severe irradiation.药物稳定 HIF-1α 可增加体内造血干细胞静止，并加速严重辐射后血液恢复。
Blood. 2013 Jan 31;121(5):759-69. doi: 10.1182/blood-2012-02-408419. Epub 2012 Dec 14.
5
Intracrine prostaglandin E(2) signalling regulates hypoxia-inducible factor-1α expression through retinoic acid receptor-β.内源性前列腺素 E(2)信号通过视黄酸受体-β调节缺氧诱导因子-1α的表达。
Int J Biochem Cell Biol. 2012 Dec;44(12):2185-93. doi: 10.1016/j.biocel.2012.08.015. Epub 2012 Aug 30.
6
Hypoxia improves expansion potential of human cord blood-derived hematopoietic stem cells and marrow repopulation efficiency.低氧环境可提高人脐血来源造血干/祖细胞的扩增潜能和骨髓重建效率。
Eur J Haematol. 2012 May;88(5):396-405. doi: 10.1111/j.1600-0609.2012.01759.x. Epub 2012 Feb 17.
7
Dynamic niches in the origination and differentiation of haematopoietic stem cells.造血干细胞起源和分化中的动态龛。
Nat Rev Mol Cell Biol. 2011 Sep 2;12(10):643-55. doi: 10.1038/nrm3184.
8
Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models.前列腺素 E2 增强了人脐血干细胞异种移植，并在临床前非人类灵长类动物移植模型中显示出长期安全性。
Cell Stem Cell. 2011 Apr 8;8(4):445-58. doi: 10.1016/j.stem.2011.02.003.
9
Regulation of the HIF-1alpha level is essential for hematopoietic stem cells.HIF-1alpha 水平的调节对造血干细胞至关重要。
Cell Stem Cell. 2010 Sep 3;7(3):391-402. doi: 10.1016/j.stem.2010.06.020.
10
The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche.造血干细胞独特的代谢特征反映了它们所处的低氧生态位位置。
Cell Stem Cell. 2010 Sep 3;7(3):380-90. doi: 10.1016/j.stem.2010.07.011.

药物增加 HIF1α 可增强造血干细胞和祖细胞归巢和植入。

Pharmacologic increase in HIF1α enhances hematopoietic stem and progenitor homing and engraftment.

机构信息

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN; and.

出版信息

Blood. 2014 Jan 9;123(2):203-7. doi: 10.1182/blood-2013-07-516336. Epub 2013 Oct 28.

DOI:10.1182/blood-2013-07-516336
PMID:24167196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3888286/
Abstract

Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for a number of immunologic disorders. For effective transplant, HSCs must traffic from the peripheral blood to supportive bone marrow niches. We previously showed that HSC trafficking can be enhanced by ex vivo treatment of hematopoietic grafts with 16-16 dimethyl prostaglandin E2 (dmPGE2). While exploring regulatory molecules involved in dmPGE2 enhancement, we found that transiently increasing the transcription factor hypoxia-inducible factor 1-α (HIF1α) is required for dmPGE2-enhanced CXCR4 upregulation and enhanced migration and homing of stem and progenitor cells and that pharmacologic manipulation of HIF1α is also capable of enhancing homing and engraftment. We also now identify the specific hypoxia response element required for CXCR4 upregulation. These data define a precise mechanism through which ex vivo pulse treatment with dmPGE2 enhances the function of hematopoietic stem and progenitor cells; these data also define a role for hypoxia and HIF1α in enhancement of hematopoietic transplantation.

摘要

造血干细胞（HSC）移植是治疗多种免疫性疾病的救命疗法。为了进行有效的移植，HSCs 必须从外周血迁移到支持性的骨髓龛位。我们之前的研究表明，通过体外处理造血移植物用 16-16 二甲基前列腺素 E2（dmPGE2）可以增强 HSC 的迁移能力。在探索与 dmPGE2 增强相关的调节分子时，我们发现短暂增加转录因子缺氧诱导因子 1-α（HIF1α）是 dmPGE2 增强 CXCR4 上调以及增强干细胞和祖细胞迁移和归巢所必需的，并且药理学操纵 HIF1α 也能够增强归巢和植入。我们现在还确定了上调 CXCR4 所需的特定缺氧反应元件。这些数据定义了一个精确的机制，通过该机制，体外脉冲处理 dmPGE2 增强了造血干细胞和祖细胞的功能；这些数据还定义了缺氧和 HIF1α 在增强造血移植中的作用。