Evaluation of cytokines for expansion of the megakaryocyte and granulocyte lineages.
Evaluation of cytokines for expansion of the megakaryocyte and granulocyte lineages.
复制标题
评估巨核细胞和粒细胞谱系扩张的细胞因子。
DOI：
10.1002/stem.150198
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Miller,WM
中科院分区：
文献类型：
--
作者：
LaIuppa,JA;Papoutsakis,ET;Miller,WM
我们研究的目标是确定可导致巨核细胞 (Mk) 和粒细胞谱系同时离体扩增的细胞因子组合，因为这些细胞类型有可能减少化疗后血小板减少症和中性粒细胞减少症的周期。我们研究了细胞因子组合对 Mk（CD41a+ 细胞和集落形成单位 [CFU]-Mk）和粒细胞（CD15+ 细胞和 CFU-粒细胞/单核细胞 [GM]）谱系扩增的影响。外周血 CD34+ 细胞在含有白细胞介素 3 (IL-3)、干细胞因子 (SCF) 以及血小板生成素 (TPO)、IL-6、GM-CSF 和/或 G-CSF 的各种组合的无血清培养基中培养。在我们的培养物中，Mk 谱系主要受 TPO 影响，尽管当 TPO 与 IL-6 组合时 Mk 和 CFU-Mk 数量有所增加。粒细胞谱系的主要刺激剂是G-CSF，尽管在添加其他因素的情况下观察到许多协同和相加效应。添加更多细胞因子后，CFU-GM 的扩增增加。 IL-3、SCF、TPO、IL-6、GM-CSF 和 G-CSF 的细胞因子组合产生最大数量的粒细胞和 CFU-GM。 Mk 和粒细胞谱系扩增所需的最低细胞因子包括 TPO 和 G-CSF，因为没有其他检查因素可以将 Mk 和粒细胞数量增加到相同程度。如果以约一升的规模产生，我们的培养系统中产生的造血祖细胞的数量应该足以在骨髓抑制治疗后成功植入。
The goal of our study was to identify cytokine combinations that would result in simultaneous ex vivo expansion of both the megakaryocyte (Mk) and granulocyte lineages, since these cell types have the potential to reduce the periods of thrombocytopenia and neutropenia following chemotherapy. We investigated the effects of cytokine combinations on expansion of the Mk (CD41a+cells and colony forming unit [CFU]-Mk) and granulocyte (CD15+cells and CFU-granulocyte/monocyte [GM]) lineages. Peripheral blood CD34+cells were cultured in serum-free medium with interleukin 3 (IL-3), stem cell factor (SCF), and various combinations of thrombopoietin (TPO), IL-6, GM-CSF, and/or G-CSF. The Mk lineage was primarily influenced by TPO in our cultures, although Mk and CFU-Mk numbers were increased when TPO was combined with IL-6. The primary stimulator of the granulocyte lineage was G-CSF, although many synergistic and additive effects were observed with addition of other factors. Expansion of CFU-GM increased upon addition of more cytokines. The cytokine combination of IL-3, SCF, TPO, IL-6, GM-CSF and G-CSF produced the greatest number of granulocytes and CFU-GM. The minimum cytokines necessary for expansion of both the Mk and granulocyte lineages included TPO and G-CSF, since no other factors examined could increase Mk and granulocyte numbers to the same extent. The number of hematopoietic progenitors produced in our culture system should be sufficient for successful engraftment following myelosuppressive therapy if produced on a scale of about one liter.