诱导多能干细胞技术在药物研发领域中的前景

The Prospect of Induction of Pluripotent Stem Cell Technology in Drug Research and Development

由于基础研究环境和临床环境之间存在的转化差异,使得药物在临床阶段取得成功仍然具有挑战性。诱导多能干(iPS)细胞的诞生为药物研发领域带来了新的希望,使研究者能在体外人性化各种药理学和毒理学模型。人iPS衍生细胞的可获得性,特别是可以定向分化成特定的功能性细胞、组织和器官,一方面为疾病机制研究与细胞治疗提供了全新的途径。另一方面,转化研究中的生物标记物提供了评估临床前基础研究环境和临床环境下毒理学及药理学影响的可衡量的指标,而iPS细胞给生物标记物的研究带来了全新的思路。从转化研究的角度概述了基于iPS细胞药物发现的现行策略,阐明了iPS细胞的潜力以及生物标志物在药物发现和发展整个过程中的作用,突出在该领域有待改进的地方,以期为进一步相关性研究提供一定参考,为新药研发提供新的思路与方法。

Despite continuous efforts to improve the process of drug discovery and development, achieving success at the clinical stageremains challenging because of a persistent translational gap between the preclinical and clinical settings. Under these circumstances, the discovery of human induced pluripotent stem （iPS） cells has brought new hope to the drug discovery field because they enable scientists to humanize a variety of pharmacological and toxicological models in vitro. Theavailability of human iPS cell-derived cells, their potential to differentiate into specific functional cells, tissues and organs, has provided new avenues for studying diseases and cell therapy. Biomarkers are an essential part of the translational effort to shift new discoveries from bench to bedside as they provide a measurable indicator to evaluate pharmacological and toxicological effects in both preclinical and clinical settings. In general, during the preclinical stage of drug development, in vitro models that are established to recapitulate human diseases are validated by using a set of biomarkers; however, their translatability to a clinical setting remains problematic. An overview of the current strategies for human iPS cellbased drug discovery from the perspective of translational research is provided.