Kaushansky K
Division of Hematology, University of Washington School of Medicine, Seattle 98195, USA.
Annu Rev Med. 1997;48:1-11. doi: 10.1146/annurev.med.48.1.1.
Until recently, platelet production was the least understood aspect of blood cell development. This gap in our understanding resulted from the scarcity of megakaryocytes, the marrow precursor of blood platelets, and from confusion surrounding the cytokines and hormones that support their development. The recent cloning and characterization of thrombopoietin (TPO) has profoundly changed our understanding of platelet production. Using in vitro assay systems, several groups have shown that TPO supports the proliferation of megakaryocytic progenitor cells and their differentiation into mature platelet-producing cells. Moreover, and somewhat surprisingly, TPO also acts in synergy with other pluripotent cytokines on the hematopoietic stem cell to augment development of erythroid and myeloid progenitors. These in vitro effects correlate well with the in vivo biology of the hormone. When administered to normal animals, TPO expands the numbers of hematopoietic progenitors of all lineages and greatly accelerates platelet production. Moreover, when TPO or its receptor is genetically eliminated, progenitor cell levels of all lineages are reduced, and platelet production is profoundly impaired. In animals administered cytoreductive therapy, the use of TPO is associated with accelerated hematopoietic recovery, not only of megakaryocytes and platelets, but also of erythrocytes and leukocytes. It, thus, is hoped that TPO may play an important role in reducing the myelosuppressive complications of naturally occurring and iatrogenic states of marrow failure.
直到最近，血小板生成仍是血细胞发育中了解最少的方面。我们在这方面认知的差距源于巨核细胞（血小板的骨髓前体细胞）的稀缺，以及围绕支持其发育的细胞因子和激素的混淆。血小板生成素（TPO）最近的克隆和特性鉴定深刻地改变了我们对血小板生成的理解。利用体外分析系统，多个研究小组表明，TPO支持巨核细胞祖细胞的增殖及其向成熟血小板生成细胞的分化。此外，有点令人惊讶的是，TPO还与其他多能细胞因子协同作用于造血干细胞，以增强红系和髓系祖细胞的发育。这些体外效应与该激素的体内生物学特性密切相关。给正常动物注射TPO时，它会增加所有谱系造血祖细胞的数量，并极大地加速血小板生成。此外，当TPO或其受体被基因敲除时，所有谱系的祖细胞水平都会降低，血小板生成也会受到严重损害。在接受细胞减灭疗法的动物中，使用TPO与加速造血恢复有关，不仅是巨核细胞和血小板的恢复，还有红细胞和白细胞的恢复。因此，人们希望TPO在减少自然发生和医源性骨髓衰竭状态的骨髓抑制并发症方面可能发挥重要作用。
