Thrombopoietin supports proliferation of human primitive hematopoietic cells in synergy with steel factor and/or interleukin-3

Thrombopoietin supports proliferation of human primitive hematopoietic cells in synergy with steel factor and/or interleukin-3
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DOI:
10.1182/blood.v88.2.429.bloodjournal882429
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发表时间:
1996-07-15
期刊:
影响因子:
20.3
通讯作者:
Ogawa, M
Ogawa, M
中科院分区:
医学1区
文献类型:
--
作者:
Kobayashi, M;Laver, JH;Ogawa, M

文献摘要

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本文研究了重组人血小板生成素(TPO; mpl ligand)对体外培养的人原始造血祖细胞增殖的影响。在TPO、Steel因子(SF)和白细胞介素-3(IL-3)的不同组合存在下,CD 34(+)/c-kit(低)/CD 38(阴性/低)细胞产生的集落少于CD 34(+)/c-kit(低)/CD 38(高)细胞。然而,当在悬浮液中培养7天并重新接种在甲基纤维素培养物中用于测量集落形成细胞时,前一群体比后者产生更多的集落形成细胞。在CD 34(+)/c-kit(低)/CD 38(阴性/低)细胞的悬浮培养中,TPO与SF和/或IL-3协同作用,支持粒细胞/巨噬细胞集落、红细胞集落和混合集落的集落形成细胞的产生。单个CD 34(+)/c-kit(低)/CD 38(阴性/低)细胞的培养研究为TPO作用的直接性质提供了证据。当与SF组合时,TPO显示出比其他早期作用因子如IL-6、IL-11和粒细胞集落刺激因子(G-CSF)更强的刺激悬浮培养中祖细胞的产生。TPO可能是造血干细胞体外操作的重要细胞因子。(C)1996年,美国血液学会。
We have studied the effects of recombinant human thrombopoietin (TPO; mpl ligand) on the proliferation of human primitive hematopoietic progenitors in vitro, CD34(+) cells were enriched for cell-cycle-dormant primitive progenitors by separation on the basis of expression of c-kit and CD38. In the presence of varying combinations of TPO, Steel factor (SF), and interleukin-3 (IL-3), CD34(+)/c-kit(low)/CD38(neg/low) cells produced fewer colonies than CD34(+)/c-kit(low)/CD38(high) cells. However, when cultured in suspension for 7 days and replated in methylcellulose culture for measurement of colony-forming cells, the former population generated more colony-forming cells than the latter. In suspension culture of CD34(+)/c-kit(low)/CD38(neg/low) cells, TPO acted synergistically with SF and/or IL-3 in support of the production of colony-forming cells for granulocyte/macrophage colonies, erythroid colonies, and mixed colonies. Culture studies of individual CD34(+)/c-kit(low)/CD38(neg/low) cells provided the evidence for the direct nature of the effects of TPO. When combined with SF, TPO showed stronger stimulation of production of progenitors in suspension culture than other early-acting factors, such as IL-6, IL-11, and granulocyte colony-stimulating factor (G-CSF). TPO may be an important cytokine for in vitro manipulation of human hematopoietic stem cells. (C) 1996 by The American Society of Hematology.