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首页> 外文期刊>Reproductive toxicology >Imatinib has deleterious effects on differentiating spermatogonia while sparing spermatogonial stem cell self renewal.
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Imatinib has deleterious effects on differentiating spermatogonia while sparing spermatogonial stem cell self renewal.

机译：伊马替尼对精原细胞的分化具有有害作用，同时保留精原干细胞的自我更新。

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摘要

Imatinib mesylate is among a growing number of effective cancer drugs that provide molecularly targeted therapy; however, imatinib causes reproductive defects in rodents. The availability of an in vitro system for screening the effect of drugs on spermatogenesis would be beneficial. The imatinib targets, KIT and platelet derived growth factor receptor beta (PDGFRB), were shown here to be expressed in "germline stem" (GS) cell cultures that contain spermatogonia, including spermatogonial stem cells (SSCs). GS cell cultures were utilized to determine whether imatinib affects SSC self renewal or differentiation. GS cells grown in imatinib retained self renewal based on multiple assays, including transplantation. However, growth in imatinib led to decreased numbers of differentiated spermatogonia and reduced culture growth consistent with the known requirement for KIT in survival and proliferation of spermatogonia. These results build upon the in vivo studies and support the possibility of utilizing GS cell cultures for preclinical drug tests.
机译：甲磺酸伊马替尼是提供分子靶向治疗的越来越多的有效抗癌药物之一。但是，伊马替尼会引起啮齿动物的生殖缺陷。用于筛选药物对精子发生作用的体外系统的可用性将是有益的。此处显示的伊马替尼靶标，KIT和血小板衍生的生长因子受体β（PDGFRB）在含有精原细胞，包括精原干细胞（SSC）的“生殖系”（GS）细胞培养物中表达。 GS细胞培养用于确定伊马替尼是否影响SSC自我更新或分化。在伊马替尼中生长的GS细胞基于包括移植在内的多种测定保留了自我更新。但是，伊马替尼的生长导致分化的精原细胞数量减少，培养物生长降低，这与已知的精原细胞生存和增殖中对KIT的要求一致。这些结果建立在体内研究的基础之上，并支持利用GS细胞培养物进行临床前药物测试的可能性。

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