A novel and simple hollow-fiber assay for in vivo evaluation of nonpeptidyl thrombopoietin receptor agonists

doi:10.1016/j.exphem.2012.01.010

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	A novel and simple hollow-fiber assay for in vivo evaluation of nonpeptidyl thrombopoietin receptor agonists
	Xie, Cheng-Ying; Xu, Yong-Ping; Zhao, Hong-Bing; Lou, Li-Guang
刊名	EXPERIMENTAL HEMATOLOGY
	2012-05
卷号	40 期号:5 页码:386-392
ISSN号	0301-472X
DOI	10.1016/j.exphem.2012.01.010
文献子类	Article
英文摘要	Preclinical in vivo assessment of the pharmacologic activity of nonpeptidyl thrombopoietin receptor (TPOR) agonists is very difficult because of the high species specificity of such agonists. In this study, we have developed a novel and simple in vivo hollow-fiber assay to preclinically evaluate TPOR agonists. The 32D-mpl cell line was generated by stable transfection of human TPOR into 32D lymphoblast cells and shown to be a specific model for nonpeptide TPOR agonists in vitro. Stably transfected 32D-mpl cells were then sealed in hollow fibers and implanted into nude mice. Cells in hollow fibers specifically responded to TPOR agonists, including thrombopoietin and eltrombopag, a nonpeptide small-molecule TPOR agonist, but not to granulocyte colony-stimulating factor or erythropoietin. Oral administration of eltrombopag stimulated 32D-mpl cell proliferation, prevented 32D-mpl cell apoptosis, and stimulated the phosphorylation of cellular signaling transducers and activators of transcription in a TPOR- and dose-dependent manner. These results indicate that the hollow-fiber assay is a specific and efficient model for rapidly evaluating the in vivo activity of small-molecule TPOR agonists. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
资助项目	National Natural Science Foundation of China[30801404]
WOS关键词	IMMUNE THROMBOCYTOPENIC PURPURA ; ELTROMBOPAG ; DISCOVERY ; CELLS ; JAK2 ; TYK2
WOS研究方向	Hematology ; Research & Experimental Medicine
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000303301100004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278098]
专题	药理学第一研究室
通讯作者	Lou, Li-Guang
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Xie, Cheng-Ying,Xu, Yong-Ping,Zhao, Hong-Bing,et al. A novel and simple hollow-fiber assay for in vivo evaluation of nonpeptidyl thrombopoietin receptor agonists[J]. EXPERIMENTAL HEMATOLOGY,2012,40(5):386-392.
APA	Xie, Cheng-Ying,Xu, Yong-Ping,Zhao, Hong-Bing,&Lou, Li-Guang.(2012).A novel and simple hollow-fiber assay for in vivo evaluation of nonpeptidyl thrombopoietin receptor agonists.EXPERIMENTAL HEMATOLOGY,40(5),386-392.
MLA	Xie, Cheng-Ying,et al."A novel and simple hollow-fiber assay for in vivo evaluation of nonpeptidyl thrombopoietin receptor agonists".EXPERIMENTAL HEMATOLOGY 40.5(2012):386-392.