Department of Medicine (Cardiology Division), University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Department of Medicine (Cardiology Division), University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Trends Cardiovasc Med. 2014 Jan;24(1):32-44. doi: 10.1016/j.tcm.2013.06.002. Epub 2013 Sep 17.
A scientific milestone that has tremendously impacted the cardiac research field has been the discovery and establishment of human-induced pluripotent stem cells (hiPSC). Key to this discovery has been uncovering a viable path in generating human patient and disease-specific cardiac cells to dynamically model and study human cardiac diseases in an in vitro setting. Recent studies have demonstrated that hiPSC-derived cardiomyocytes can be used to model and recapitulate various known disease features in hearts of patient donors harboring genetic-based cardiac diseases. Experimental drugs have also been tested in this setting and shown to alleviate disease phenotypes in hiPSC-derived cardiomyocytes, further paving the way for therapeutic interventions for cardiac disease. Here, we review state-of-the-art methods to generate high-quality hiPSC and differentiate them towards cardiomyocytes as well as the full range of genetic-based cardiac diseases, which have been modeled using hiPSC. We also provide future perspectives on exploiting the potential of hiPSC to compliment existing studies and gain new insights into the mechanisms underlying cardiac disease.
一个具有重大影响的医学研究领域的科学里程碑是人类诱导多能干细胞(hiPSC)的发现和建立。这一发现的关键在于找到了一条可行的途径,可以生成人类患者和疾病特异性的心脏细胞,以便在体外环境中动态模拟和研究人类心脏疾病。最近的研究表明,hiPSC 衍生的心肌细胞可用于模拟和再现携带基于遗传的心脏疾病的患者供体心脏中的各种已知疾病特征。在这种情况下,也已经测试了实验药物,并显示出可减轻 hiPSC 衍生的心肌细胞中的疾病表型,进一步为心脏疾病的治疗干预铺平了道路。在这里,我们回顾了生成高质量 hiPSC 并将其分化为心肌细胞的最新方法,以及使用 hiPSC 模拟的各种基于遗传的心脏疾病。我们还提供了利用 hiPSC 的潜力来补充现有研究并深入了解心脏疾病潜在机制的未来展望。