Cell Stem Cell：利用干细胞制造出的心肌细胞有助精准心血管医疗取得进展

Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro

在一项新的研究中。来自美国斯坦福大学医学院的研究人员发现利用人诱导性多能干细胞（iPS细胞）制造的心肌细胞忠实地反映供者天然的心脏组织中关键基因的表达模式。因此，这些细胞能够被用来预测病人是否可能经历药物相关的心脏损伤。相关研究结果在线发表在Cell Stem Cell期刊上。论文标题为＂Transcriptome Profiling of Patient -Specific Human iPSC - ardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro＂.

Understanding individual susceptibility to drug-induced cardiotoxicity is key to improving patient safety and preventing drug attrition. Human induced pluripotent stem cells (hiPSCs) enable the study of pharmacological and toxicological responses in patient-specific cardiomyocytes (CMs) and may serve as preclinical platforms for precision medicine. Transcriptome profiling in hiPSC-CMs from seven individuals lacking known cardiovascular disease-associated mutations and in three isogenic human heart tissue and hiPSC-CM pairs showed greater inter-patient variation than intra-patient variation, verifying that reprogramming and differentiation preserve patient-specific gene expression, particularly in metabolic and stress-response genes. Transcriptome-based toxicology analysis predicted and risk-stratified patient-specific susceptibility to cardiotoxicity, and functional assays in hiPSC-CMs using tacrolimus and rosiglitazone, drugs targeting pathways predicted to produce cardiotoxicity, validated inter-patient differential responses. CRISPR/Cas9-mediated pathway correction prevented drug-induced cardiotoxicity. Our data suggest that hiPSC-CMs can be used in vitro to predict and validate patient-specific drug safety and efficacy, potentially enabling future clinical approaches to precision medicine.