Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Biochem Pharmacol. 2019 Nov;169:113624. doi: 10.1016/j.bcp.2019.113624. Epub 2019 Aug 29.
Hematopoietic stem cell transplantation (HSCT) plays an important role in the therapy of hematological malignancies and some nonmalignant diseases. Granulocyte colony-stimulating factor (G-CSF) is generally used to mobilize and collect hematopoietic stem cells from donors and accelerate neutrophil recovery in transplantation recipients. However, less attention has been paid to the fact that G-CSF administration might result in thrombocytopenia and enhance bleeding risk in HSCT. In this study, we investigated the effects of G-CSF on platelet counts in healthy mice and mice that received bone marrow transplantation. It was observed that G-CSF administration induced thrombocytopenia in healthy mice and aggravated thrombocytopenia in mice that received bone marrow transplantation. Furthermore, we analyzed the regulatory effects of G-CSF on the differentiation of hematopoietic progenitors and megakaryocytes, and activation of platelets and endothelial cells. The results reveal that G-CSF administration causes thrombocytopenia mainly by inhibiting the differentiation of common myeloid progenitors and megakaryotic erythroid progenitors into megakaryocytes and platelet formation but not through enhancing activation of platelets or endothelial cells and following platelet consumption. Collectively, G-CSF administration can result in thrombocytopenia in hematopoietic stem cell donors and exacerbate existing thrombocytopenia in transplantation recipients. More attention should be paid to bleeding risk of G-CSF administration in HSCT, especially autologous HSCT.
造血干细胞移植（HSCT）在血液系统恶性肿瘤和一些非恶性疾病的治疗中起着重要作用。粒细胞集落刺激因子（G-CSF）通常用于动员和采集供者的造血干细胞，并加速移植受者中性粒细胞的恢复。然而，人们较少关注到 G-CSF 给药可能导致血小板减少，并增强 HSCT 中的出血风险。在这项研究中，我们研究了 G-CSF 对健康小鼠和接受骨髓移植小鼠血小板计数的影响。结果观察到 G-CSF 给药诱导健康小鼠血小板减少，并加重接受骨髓移植小鼠的血小板减少。此外，我们分析了 G-CSF 对造血祖细胞和巨核细胞分化以及血小板和内皮细胞激活的调节作用。结果表明，G-CSF 给药导致血小板减少主要是通过抑制共同髓系祖细胞和巨核红细胞祖细胞向巨核细胞和血小板形成的分化，而不是通过增强血小板或内皮细胞的激活和随后的血小板消耗。总之，G-CSF 给药可导致造血干细胞供者发生血小板减少，并加重移植受者的现有血小板减少。在 HSCT 中，特别是自体 HSCT 中，应更加关注 G-CSF 给药的出血风险。
