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造血体外模型在药物研发中的开发与应用。

Development and application of in vitro models of hematopoiesis to drug development.

作者信息

Deldar A, Stevens C E

机构信息

In Vitro Hematopoiesis Laboratory, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, Indiana 46140.

出版信息

Toxicol Pathol. 1993;21(2):231-40. doi: 10.1177/019262339302100216.

DOI:10.1177/019262339302100216
PMID:7692585
Abstract

In vitro models of hematopoiesis are used increasingly in investigative hematopathology. Such models complement in vivo animal testing and have been shown to be predictive for hematotoxicity associated with anticancer and antiviral agents in humans. In vitro models of hematopoiesis consist of short-term cloning assays for various hematopoietic progenitor cells and long-term functional assays for the marrow hematopoietic microenvironment. In our laboratories, the cloning assays have been used as investigative tools to study the pathogenetic mechanisms of drug-induced blood disorders and as screening systems to investigate the possible hematotoxic potential of candidate drugs in various animal species. Data in support of these applications are presented in this paper.

摘要

造血的体外模型在血液病理学研究中的应用日益广泛。此类模型可补充体内动物试验,并且已证明能够预测人类中与抗癌和抗病毒药物相关的血液毒性。造血的体外模型包括针对各种造血祖细胞的短期克隆测定以及针对骨髓造血微环境的长期功能测定。在我们实验室中,克隆测定已被用作研究药物诱导的血液疾病发病机制的研究工具,以及作为研究各种动物物种中候选药物可能的血液毒性潜力的筛选系统。本文展示了支持这些应用的数据。

相似文献

1
Development and application of in vitro models of hematopoiesis to drug development.造血体外模型在药物研发中的开发与应用。
Toxicol Pathol. 1993;21(2):231-40. doi: 10.1177/019262339302100216.
2
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3
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Int Rev Exp Pathol. 1993;34 Pt A:215-33.
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AM5, a protein-associated polysaccharide, stimulates hematopoiesis and modulates the expression of endogenous hematopoietic growth factors in murine long-term bone marrow cultures.AM5是一种与蛋白质相关的多糖,可刺激造血,并调节小鼠长期骨髓培养物中内源性造血生长因子的表达。
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Exp Hematol. 1997 Mar;25(3):252-5.

引用本文的文献

1
Alternative testing systems for evaluating noncarcinogenic, hematologic toxicity.用于评估非致癌性血液毒性的替代测试系统。
Environ Health Perspect. 1998 Apr;106 Suppl 2(Suppl 2):541-57. doi: 10.1289/ehp.98106541.
2
A cellular model for drug interactions on hematopoiesis: the use of human umbilical cord blood progenitors as a model for the study of drug-related myelosuppression of normal hematopoiesis.一种药物对造血作用的细胞模型:利用人脐带血祖细胞作为研究药物相关正常造血骨髓抑制的模型。
Cell Biol Toxicol. 1996 Feb;12(1):39-53. doi: 10.1007/BF00143393.
3
In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans.
抗病毒药物对造血祖细胞集落形成的体外抑制效力与人类免疫缺陷病毒阳性患者血液毒性水平下的暴露情况相关。
Antimicrob Agents Chemother. 1996 Feb;40(2):514-9. doi: 10.1128/AAC.40.2.514.