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使用实验性小鼠模型评估造血干细胞和祖细胞动员的新型药物。

The use of experimental murine models to assess novel agents of hematopoietic stem and progenitor cell mobilization.

作者信息

Herbert Kirsten E, Lévesque Jean-Pierre, Haylock David N, Prince H Miles

机构信息

Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.

出版信息

Biol Blood Marrow Transplant. 2008 Jun;14(6):603-21. doi: 10.1016/j.bbmt.2008.02.003.

DOI:10.1016/j.bbmt.2008.02.003
PMID:18489986
Abstract

The recent explosion in the understanding of the cellular and molecular mechanisms underlying hematopoietic stem and progenitor cell (HSPC) mobilization has facilitated development of novel therapeutic agents, targeted at improving mobilization kinetics as well as HSPC yield. With the development of new agents comes the challenge of choosing efficient and relevant preclinical studies for the testing of the HSPC mobilization efficacy of these agents. This article reviews the use of the mouse as a convenient small animal model of HSPC mobilization and transplantation, and outlines the range of murine assays that can be applied to assess novel HSPC mobilizing agents. Techniques to demonstrate murine HSPC mobilization are discussed, as well as the role of murine assays to confirm human HSPC mobilization, and techniques to investigate the biologic phenotype of HSPC mobilized by these novel agents. Technical aspects regarding mobilization regimens and control arms, and choice of experimental animals are also discussed.

摘要

最近,人们对造血干细胞和祖细胞(HSPC)动员背后的细胞和分子机制的理解有了飞跃,这推动了新型治疗药物的研发,这些药物旨在改善动员动力学以及HSPC产量。随着新药物的出现,为测试这些药物的HSPC动员效果而选择高效且相关的临床前研究成为一项挑战。本文综述了将小鼠作为HSPC动员和移植的便捷小动物模型的应用,并概述了可用于评估新型HSPC动员剂的一系列小鼠试验。文中讨论了证明小鼠HSPC动员的技术,以及小鼠试验在确认人类HSPC动员方面的作用,还有研究这些新型药物动员的HSPC生物学表型的技术。还讨论了动员方案和对照臂的技术方面以及实验动物的选择。

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The use of experimental murine models to assess novel agents of hematopoietic stem and progenitor cell mobilization.使用实验性小鼠模型评估造血干细胞和祖细胞动员的新型药物。
Biol Blood Marrow Transplant. 2008 Jun;14(6):603-21. doi: 10.1016/j.bbmt.2008.02.003.
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Stem Cell Res Ther. 2021 Jan 7;12(1):17. doi: 10.1186/s13287-020-02073-z.
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The potential of non-myeloablative heterochronous autologous hematopoietic stem cell transplantation for extending a healthy life span.非清髓性异时自体造血干细胞移植延长健康寿命的潜力。
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Inducible disruption of the c-myb gene allows allogeneic bone marrow transplantation without irradiation.
c-myb基因的可诱导性破坏使得异基因骨髓移植无需进行辐射。
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Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization.小鼠原代造血干细胞的磷酸化蛋白质组分析揭示了造血干细胞动员的新调节因子。
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Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist.使用小分子整合素拮抗剂对骨内膜造血干细胞进行治疗靶向和快速动员。
Nat Commun. 2016 Mar 15;7:11007. doi: 10.1038/ncomms11007.