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嘌呤能信号转导及其在骨髓干细胞动员中的作用。

Purinergic Signaling and Its Role in Mobilization of Bone Marrow Stem Cells.

机构信息

Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Department of Molecular Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.

出版信息

Methods Mol Biol. 2023;2567:263-280. doi: 10.1007/978-1-0716-2679-5_17.

DOI:10.1007/978-1-0716-2679-5_17
PMID:36255707
Abstract

Mobilization or egress of stem cells from bone marrow (BM) into peripheral blood (PB) is an evolutionary preserved and important mechanism in an organism for self-defense and regeneration. BM-derived stem cells circulate always at steady-state conditions in PB, and their number increases during stress situations related to (a) infections, (b) tissue organ injury, (c) stress, and (d) strenuous exercise. Stem cells also show a circadian pattern of their PB circulating level with peak in early morning hours and nadir late at night. The number of circulating in PB stem cells could be pharmacologically increased after administration of some drugs such as cytokine granulocyte colony-stimulating factor (G-CSF) or small molecular antagonist of CXCR4 receptor AMD3100 (Plerixafor) that promote their egress from BM into PB and lymphatic vessels. Circulating can be isolated from PB for transplantation purposes by leukapheresis. This important homeostatic mechanism is governed by several intrinsic complementary pathways. In this chapter, we will discuss the role of purinergic signaling and extracellular nucleotides in regulating this process and review experimental strategies to study their involvement in mobilization of various types of stem cells that reside in murine BM.

摘要

骨髓(BM)中的干细胞向外周血(PB)的动员或迁出是生物体自我防御和再生的一种进化上保守且重要的机制。在 PB 中,BM 来源的干细胞始终处于稳定状态循环,并且在与(a)感染、(b)组织器官损伤、(c)应激和(d)剧烈运动相关的应激情况下其数量会增加。干细胞的 PB 循环水平也存在昼夜节律模式,峰值出现在清晨,低谷出现在深夜。一些药物(如细胞因子粒细胞集落刺激因子(G-CSF)或 CXCR4 受体小分子拮抗剂 AMD3100(plerixafor))给药后,干细胞向 PB 和淋巴管的迁出会增加 PB 中循环的干细胞数量,从而增加其数量。可以通过白细胞分离术从 PB 中分离出用于移植的循环细胞。这种重要的体内平衡机制受几个内在互补途径的控制。在本章中,我们将讨论嘌呤能信号转导和细胞外核苷酸在调节这一过程中的作用,并综述研究其在各种驻留在鼠 BM 中的干细胞动员中的作用的实验策略。

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本文引用的文献

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The Nlrp3 inflammasome as a "rising star" in studies of normal and malignant hematopoiesis.Nlrp3 炎性小体作为正常和恶性造血研究中的“后起之秀”。
Leukemia. 2020 Jun;34(6):1512-1523. doi: 10.1038/s41375-020-0827-8. Epub 2020 Apr 20.
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Purine and purinergic receptors.嘌呤与嘌呤能受体。
Brain Neurosci Adv. 2018 Dec 6;2:2398212818817494. doi: 10.1177/2398212818817494. eCollection 2018 Jan-Dec.
3
Novel Evidence that Purinergic Signaling - Nlrp3 Inflammasome Axis Regulates Circadian Rhythm of Hematopoietic Stem/Progenitor Cells Circulation in Peripheral Blood.
嘌呤能信号-NLRP3 炎性小体轴调控造血干细胞/祖细胞在外周血循环中的生物钟。
Stem Cell Rev Rep. 2020 Apr;16(2):335-343. doi: 10.1007/s12015-020-09953-0.
4
The Inhibition of CD39 and CD73 Cell Surface Ectonucleotidases by Small Molecular Inhibitors Enhances the Mobilization of Bone Marrow Residing Stem Cells by Decreasing the Extracellular Level of Adenosine.小分子抑制剂抑制 CD39 和 CD73 细胞表面核苷酸酶,通过降低细胞外腺苷水平增强骨髓驻留干细胞的动员。
Stem Cell Rev Rep. 2019 Dec;15(6):892-899. doi: 10.1007/s12015-019-09918-y.
5
The Nlrp3 Inflammasome Orchestrates Mobilization of Bone Marrow-Residing Stem Cells into Peripheral Blood.NLRP3 炎性小体协调骨髓驻留干细胞向外周血的动员。
Stem Cell Rev Rep. 2019 Jun;15(3):391-403. doi: 10.1007/s12015-019-09890-7.
6
Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells.靶向 VLA4 整合素和 CXCR2 动员连续再殖造血干细胞。
J Clin Invest. 2019 May 14;129(7):2745-2759. doi: 10.1172/JCI124738.
7
NLRP3 inflammasome couples purinergic signaling with activation of the complement cascade for the optimal release of cells from bone marrow.NLRP3 炎性小体将嘌呤能信号与补体级联的激活偶联起来,以实现骨髓细胞的最佳释放。
Leukemia. 2019 Apr;33(4):815-825. doi: 10.1038/s41375-019-0436-6. Epub 2019 Mar 7.
8
Poor mobilizer and its countermeasures.动员能力差及其应对措施。
Transfus Apher Sci. 2018 Oct;57(5):623-627. doi: 10.1016/j.transci.2018.09.007. Epub 2018 Sep 11.
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The Emerging Link Between the Complement Cascade and Purinergic Signaling in Stress Hematopoiesis.应激造血中补体级联反应与嘌呤能信号传导之间的新联系。
Front Immunol. 2018 Jun 5;9:1295. doi: 10.3389/fimmu.2018.01295. eCollection 2018.
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