Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0671, USA.
Hematology Am Soc Hematol Educ Program. 2009:147-52. doi: 10.1182/asheducation-2009.1.147.
Our understanding of thrombopoiesis has improved greatly in the last two decades with the availability of in vitro assays of megakaryocyte progenitor cell growth, with the cloning and characterization of stem cell factor (SCF) and thrombopoietin (Tpo), the latter the primary humoral regulator of this process, and with the generation of genetically altered murine models of thrombopoietic failure and excess. While SCF affects developmentally early aspects of megakaryocyte growth, Tpo affects nearly all aspects of platelet production, from hematopoietic stem cell (HSC) self-renewal and expansion, through stimulation of megakaryocyte progenitor cell proliferation, to supporting their maturation into platelet-producing cells. The molecular and cellular mechanisms through which the marrow microenvironment and humoral mediators affect platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis, and highlight new opportunities to translate basic biology into clinical advances.
在过去的二十年中，随着巨核细胞祖细胞生长的体外检测方法的出现，随着干细胞因子 (SCF) 和血小板生成素 (Tpo) 的克隆和特性描述，后者是该过程的主要体液调节剂，以及生成遗传改变的巨核细胞生成失败和过度的小鼠模型，我们对血栓形成的理解有了很大的提高。虽然 SCF 影响巨核细胞生长的早期发育阶段，但 Tpo 几乎影响血小板生成的所有方面，从造血干细胞 (HSC) 的自我更新和扩增，通过刺激巨核细胞祖细胞的增殖，到支持它们成熟为产生血小板的细胞。骨髓微环境和体液介质影响血小板生成的分子和细胞机制为内在和外在因素对造血的相互作用提供了新的见解，并强调了将基础生物学转化为临床进展的新机会。
