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血小板生成

Thrombopoiesis.

作者信息

Kaushansky Kenneth

机构信息

School of Medicine, Stony Brook University, Stony Brook, NY.

出版信息

Semin Hematol. 2015 Jan;52(1):4-11. doi: 10.1053/j.seminhematol.2014.10.003. Epub 2014 Oct 31.

Abstract

The production of platelets is a complex process that involves hematopoietic stem cells (HSCs), their differentiated progeny, the marrow microenvironment and hematopoietic cytokines. Much has been learned in the 110 years since James Homer Wright postulated that marrow megakaryocytes were responsible for blood platelet production, at a time when platelets were termed the "dust of the blood". In the 1980s a number of in vitro culture systems were developed that could produce megakaryocytes, followed by the identification of several cytokines that could stimulate the process in vitro. However, none of these cytokines produced a substantial thrombocytosis when injected into animals or people, nor were blood levels inversely related to platelet count, the sine qua non of a physiological regulator. A major milestone in our understanding of thrombopoiesis occurred in 1994 when thrombopoietin, the primary regulator of platelet production was cloned and initially characterized. Since that time many of the molecular mechanisms of thrombopoiesis have been identified, including the effects of thrombopoietin on the survival, proliferation, and differentiation of hematopoietic stem and progenitor cells, the development of polyploidy and proplatelet formation, the final fragmentation of megakaryocyte cytoplasm to yield blood platelets, and the regulation of this process. While much progress has been made, several outstanding questions remain, such as the nature of the signals for final platelet formation, the molecular nature of the regulation of marrow stromal thrombopoietin production, and the role of these physiological processes in malignant hematopoiesis.

摘要

血小板的生成是一个复杂的过程,涉及造血干细胞(HSCs)、其分化的子代细胞、骨髓微环境和造血细胞因子。自詹姆斯·霍默·赖特提出骨髓巨核细胞负责血小板生成以来的110年里,我们已经了解了很多情况,当时血小板被称为“血液中的尘埃”。在20世纪80年代,开发了一些能够产生巨核细胞的体外培养系统,随后鉴定出了几种能够在体外刺激这一过程的细胞因子。然而,将这些细胞因子注射到动物或人体内时,没有一种能产生显著的血小板增多,而且血液水平也与血小板计数没有负相关,而这是生理调节因子的必要条件。1994年,我们对血小板生成的理解取得了一个重大里程碑,当时克隆并初步鉴定了血小板生成素,即血小板生成的主要调节因子。从那时起,已经确定了血小板生成的许多分子机制,包括血小板生成素对造血干细胞和祖细胞的存活、增殖和分化的影响,多倍体的发育和前血小板的形成,巨核细胞胞质最终破碎以产生血小板,以及这一过程的调节。虽然已经取得了很大进展,但仍有几个突出问题,例如最终血小板形成的信号性质、骨髓基质血小板生成素产生调节的分子性质,以及这些生理过程在恶性造血中的作用。

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