魚崎 英毅 自治医科大学分子病態治療研究センター再生医学研究部 准教授はじめに実験方法結果及び考察1. Morphology & Structure: ― 297 ―Mitochondrial diseases are complex disorders caused by mutations in either nuclear or mitochondrial DNA, causing reduced mitochondrial function. Approximately 20-40% of children affected by mitochondrial diseases experience heart dysfunction known as mitochondrial cardiomyopathy (MCM), which significantly raises mortality rates and currently lacks targeted treatments1). Research on MCM has been limited due to the reliance on donor fibroblasts rather than cardiomyocytes2). In this project, we aimed to establish an MCM-induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs) disease model library for drug development and fundamental research of the disease mechanisms.I used iPSC lines generated from fibroblasts of more than 20 patients with mitochondrial diseases and differentiated them into cardiomyocytes. I used my recently developed adeno-associated virus-based purification method to select iPSC-CMs3). After purification, I examined the characteristics of these MCM-iPSC-CMs by assessing their morphology, structure, reactive oxygen species (ROS) production, calcium handling, and contractile function. MCM usually manifests as hypertrophic or dilated cardiomyopathy. Some MCM-iPSC-CMs showed significant hypertrophy shortly after differentiation (Figure 1). Additionally, hypertrophic cells displayed disorganized or absent sarcomeres (Figure 2).2. ROS Production: Despite the lack of statistical significance, some MCM-iPSC-CMs lines showed upward trends in ROS production (Figure 3). Data sets are not complete yet. To note, results may be biased due to the presence of antioxidants in the culture medium.Generation of mitochondrial cardiomyopathy models using patient-derived induced pluripotent stem cells as a platform for testing drug efficacy.Ahmed Razan2022.4 ～ 2024.3
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