Department of Applied Stem Cell Technologies, TechMed Centre, University of Twente, Drienerlolaan 5, 7500AE Enschede, the Netherlands.
Department of Applied Stem Cell Technologies, TechMed Centre, University of Twente, Drienerlolaan 5, 7500AE Enschede, the Netherlands; Department of Anatomy and Embryology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands.
Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165881. doi: 10.1016/j.bbadis.2020.165881. Epub 2020 Jun 17.
Patient-derived human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are increasingly being used for disease modeling, drug screening and regenerative medicine. However, to date, an immature, fetal-like, phenotype of hPSC-CMs restrains their full potential. Increasing evidence suggests that the metabolic state, particularly important for provision of sufficient energy in highly active contractile CMs and anabolic and regulatory processes, plays an important role in CM maturation, which affects crucial functional aspects of CMs, such as contractility and electrophysiology. During embryonic development the heart is subjected to metabolite concentrations that differ substantially from that of hPSC-derived cardiac cell cultures. A deeper understanding of the environmental and metabolic cues during embryonic heart development and how these change postnatally, will provide a framework for optimizing cell culture conditions and maturation of hPSC-CMs. Maturation of hPSC-CMs will improve the predictability of disease modeling, drug screening and drug safety assessment and broadens their applicability for personalized and regenerative medicine.
患者来源的人多能干细胞衍生的心肌细胞（hPSC-CMs）越来越多地被用于疾病建模、药物筛选和再生医学。然而，迄今为止，hPSC-CMs 表现出一种不成熟的、胎儿样的表型，限制了它们的全部潜力。越来越多的证据表明，代谢状态，特别是对高度活跃的收缩性心肌细胞提供足够能量和合成代谢及调节过程非常重要，在 CM 成熟中起着重要作用，这影响 CM 的关键功能方面，如收缩性和电生理学。在胚胎发育过程中，心脏受到的代谢物浓度与 hPSC 衍生的心脏细胞培养物中的浓度有很大的不同。深入了解胚胎心脏发育过程中的环境和代谢线索，以及这些线索在出生后的变化，将为优化细胞培养条件和 hPSC-CMs 的成熟提供框架。hPSC-CMs 的成熟将提高疾病建模、药物筛选和药物安全性评估的可预测性，并拓宽其在个性化和再生医学中的适用性。
