Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.
Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.
复制标题
DOI：
10.1080/17425255.2021.1894122
复制
发表时间：
2021-08
影响因子：
4.3
通讯作者：
Rusyn I
中科院分区：
文献类型：
--
作者：
Burnett SD;Blanchette AD;Chiu WA;Rusyn I
人类诱导多能干细胞（iPSC）衍生的心肌细胞是最广泛使用的基于细胞的模型之一，其源于发现非胚胎干细胞如何分化为多种细胞类型。在短短十年内，iPSC衍生的心肌细胞从研究实验室广泛用于药物和其他化学品的生物医学研究和临床前安全性评估。本文综述了人类iPSC衍生心肌细胞的毒理学应用数据。我们详细介绍了系统性文献检索的结果，其使用（i）在心脏毒性责任的危害评估，（ii）风险表征，（iii）作为人口变异性的模型，（iv）在个性化医疗和疾病的研究。iPSC衍生的心肌细胞可用于提高药物和非药物的心脏毒性危害识别的准确性、精确度和效率，最近的努力开始证明其用于风险表征的实用性。值得注意的局限性包括需要提高培养中细胞的成熟度，更好地了解其识别结构性心脏毒性的潜在用途，以及涉及人群范围和疾病特异性风险表征的其他病例研究。最终，未来最大的好处可能是非药物化学品，填补了目前没有进行心脏毒性常规测试的关键空白。
Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes is one of the most widely used cell-based models that resulted from the discovery of how non-embryonic stem cells can be differentiated into multiple cell types. In just one decade, iPSC-derived cardiomyocytes went from a research lab to widespread use in biomedical research and preclinical safety evaluation for drugs and other chemicals. This manuscript reviews data on toxicology applications of human iPSC-derived cardiomyocytes. We detail the outcome of a systematic literature search on their use (i) in hazard assessment for cardiotoxicity liabilities, (ii) for risk characterization, (iii) as models for population variability, and (iv) in studies of personalized medicine and disease. iPSC-derived cardiomyocytes are useful to increase the accuracy, precision, and efficiency of cardiotoxicity hazard identification for both drugs and non-pharmaceuticals, with recent efforts beginning to demonstrate their utility for risk characterization. Notable limitations include the needs to improve the maturation of cells in culture, to better understand their potential use identifying structural cardiotoxicity, and for additional case studies involving population-wide and disease-specific risk characterization. Ultimately, the greatest future benefits are likely for non-pharmaceutical chemicals, filling a critical gap where no routine testing for cardiotoxicity is currently performed.
登录
查看更多内容
影响因子：
3.8
作者：
Cohen JD;Babiarz JE;Abrams RM;Guo L;Kameoka S;Chiao E;Taunton J;Kolaja KL
通讯作者：
Kolaja KL
DOI：
10.1186/s40959-017-0025-7
发表时间：
2017-01-01
期刊：
Cardio-oncology (London, England)
影响因子：
--
作者：
Clark, Robyn A;Marin, Tania S;Koczwara, Bogda
通讯作者：
Koczwara, Bogda
影响因子：
6.7
作者：
Blanchette, Alexander D.;Grimm, Fabian A.;Chiu, Weihsueh A.
通讯作者：
Chiu, Weihsueh A.
影响因子：
6.1
作者：
Arrigoni, C.;Crivori, P.
通讯作者：
Crivori, P.
影响因子：
37.8
作者：
Bonaca, Marc P.;Olenchock, Benjamin A.;Moslehi, Javid
通讯作者：
Moslehi, Javid