Evaluating the utility of cardiomyocytes from human pluripotent stem cells for drug screening
Evaluating the utility of cardiomyocytes from human pluripotent stem cells for drug screening
复制标题
DOI：
10.1042/bst0381037
复制
发表时间：
2010-08-01
影响因子：
3.9
通讯作者：
Denning, Chris
中科院分区：
文献类型：
--
作者：
Dick, Emily;Rajamohan, Divya;Denning, Chris
功能性心肌细胞现在可以常规地源自 hPSC（人类多能干细胞），hPSC 统称为胚胎干细胞和诱导多能干细胞。该技术为开发药理学相关的体外筛选来检测心脏毒性提供了新的机会，以提高患者的安全性，同时减少高药物损耗率给行业带来的经济负担。在本文中，我们考虑了药物筛选活动中对人类心肌细胞的需求，并回顾了用于将 hPSC 分化为心脏谱系的策略。在分化离子的早期阶段，hPSC 心肌细胞表现出基因表达谱、超微结构、离子通道功能和药理学反应，让人想起胚胎表型，但在长时间培养期间的成熟已得到令人信服的证明。值得注意的是，hPSC 心肌细胞已被证明能够以高度可预测的方式对 40 多种化合物产生反应，这些化合物对人类心脏具有已知的药理作用。这表明有必要进一步开发和验证 hPSC 心肌细胞模型作为评估心脏毒性的工具。
Functional cardiomyocytes can now be derived routinely from hPSCs (human pluripotent stem cells), which collectively include embryonic and induced pluripotent stem cells. This technology presents new opportunities to develop pharmacologically relevant in vitro screens to detect cardiotoxicity, with a view to improving patient safety while reducing the economic burden to industry arising from high drug attrition rates. In the present article, we consider the need for human cardiomyocytes in drug-screening campaigns and review the strategies used to differentiate hPSCs towards the cardiac lineage. During early stages of differential ion, hPSC-cardiomyocytes display gene expression profiles, ultra-structures, ion channel functionality and pharmacological responses reminiscent of an embryonic phenotype, but maturation during extended time in culture has been demonstrated convincingly. Notably, hPSC-cardiomyocytes have been shown to respond in a highly predictable manner to over 40 compounds that have a known pharmacological effect on the human heart. This suggests that further development and validation of the hPSC-cardiomyocyte model as a tool for assessing cardiotoxicity is warranted.