Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; The Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Stem Cell Reports. 2021 Mar 9;16(3):519-533. doi: 10.1016/j.stemcr.2021.01.018. Epub 2021 Feb 25.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease. Here, we sought to develop a simple method that could drive cultured hiPSC-CMs toward maturity across a number of phenotypes, with the aim of utilizing mature hiPSC-CMs to model human cardiovascular disease. hiPSC-CMs were cultured in fatty acid-based medium and plated on micropatterned surfaces. These cells display many characteristics of adult human cardiomyocytes, including elongated cell morphology, sarcomeric maturity, and increased myofibril contractile force. In addition, mature hiPSC-CMs develop pathological hypertrophy, with associated myofibril relaxation defects, in response to either a pro-hypertrophic agent or genetic mutations. The more mature hiPSC-CMs produced by these methods could serve as a useful in vitro platform for characterizing cardiovascular disease.
人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）是生物医学研究的强大平台。然而，它们不成熟，这是建模成人发病心血管疾病的障碍。在这里，我们试图开发一种简单的方法，可以使培养的 hiPSC-CMs 在许多表型上向成熟方向发展，目的是利用成熟的 hiPSC-CMs 来模拟人类心血管疾病。hiPSC-CMs 在基于脂肪酸的培养基中培养，并铺在微图案化表面上。这些细胞表现出许多成年人心肌细胞的特征，包括伸长的细胞形态、肌节成熟和增加的肌原纤维收缩力。此外，成熟的 hiPSC-CMs 对促肥大剂或基因突变会产生病理性肥大，并伴有肌原纤维弛豫缺陷。通过这些方法产生的更成熟的 hiPSC-CMs 可以作为一个有用的体外平台，用于表征心血管疾病。
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