Department of Clinical Genetics, Maastricht University Medical Center+, Maastricht, the Netherlands.
Department of Clinical Genetics, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Genetics & Cell Biology, Maastricht University Medical Center+ and FHML, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
Prostaglandins Leukot Essent Fatty Acids. 2021 Apr;167:102267. doi: 10.1016/j.plefa.2021.102267. Epub 2021 Mar 13.
Isolated or cultured cells have proven to be valuable model systems to investigate cellular (patho)biology and for screening of the efficacy of drugs or their possible side-effects. Pluripotent stem cells (PSC) can be readily obtained from healthy individuals as well as from diseased patients, and protocols have been developed to differentiate these cells into cardiomyocytes. Hence, these cellular models are moving center stage for a broader application. In this review, we focus on comparing mouse HL-1 cardiomyocytes, isolated adult rat cardiomyocytes, human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for the study of metabolic aspects of cardiac functioning in health and disease. Various studies have reported that these cellular models are suitable for assessing substrate uptake and utilization, in that each display an adequate and similar response to physiological triggers, in particular the presence of insulin. Likewise, disease conditions, such as excess lipid supply, similarly affect each of these rodent and human cardiomyocyte models. It is concluded that PSC-CMs obtained from patients with cardiogenetic abnormalities are promising models to evaluate the functional consequence of gene variants with unknown significance.
已证明，分离或培养的细胞是研究细胞（病理）生物学以及筛选药物疗效及其可能副作用的有价值的模型系统。多能干细胞 (PSC) 可轻易从健康个体以及患病患者中获得，并且已经开发出将这些细胞分化为心肌细胞的方案。因此，这些细胞模型正在更广泛的应用中占据中心舞台。在这篇综述中，我们专注于比较小鼠 HL-1 心肌细胞、分离的成年大鼠心肌细胞、人类胚胎干细胞衍生的心肌细胞 (hESC-CMs) 和人类诱导多能干细胞衍生的心肌细胞 (hiPSC-CMs)，以研究心脏功能在健康和疾病中的代谢方面。多项研究报告称，这些细胞模型适合评估底物摄取和利用，因为每种模型对生理触发因素（特别是胰岛素的存在）都有足够且相似的反应。同样，疾病状况，如脂质供应过剩，也会对这些啮齿动物和人类心肌细胞模型产生类似的影响。结论是，从患有遗传性心脏病的患者中获得的 PSC-CMs 是评估具有未知意义的基因变异的功能后果的有前途的模型。
