UNASSIGNED: A fatty acid-containing medium was developed based on an analysis of fatty acid consumption by rat primary cardiomyocytes (rat-CMs), and the effects of this medium on adenosine triphosphate (ATP) production were investigated through bioluminescence imaging of luciferase-expressing rat-CMs. Next, the fatty acid content of the medium was further adjusted based on analyses of fatty acid utilization by porcine hearts and hiPSC-CMs. Oxygen consumption analyses were performed to explore whether the fatty acid-containing medium induced hiPSC-CMs to switch from anaerobic metabolism to aerobic metabolism. Furthermore, the effects of the medium on contractile force generated by hiPSC-CM-derived tissue were evaluated.
UNASSIGNED: Rat serum, human serum and porcine plasma contained similar types of fatty acid (oleic acid, stearic acid, linoleic acid, palmitic acid and arachidonic acid). The types of fatty acid consumed were also similar between rat-CMs, hiPSC-CMs and porcine heart. The addition of fatty acids to the culture medium increased the bioluminescence of luciferase-expressing rat-CMs (an indirect measure of ATP level), oxygen consumption by hiPSC-CMs, and contractile force generated by cardiac tissues constructed from hiPSC-CMs.
UNASSIGNED: hiPSC-CMs metabolize similar types of fatty acid to those consumed by rat-CMs and porcine hearts. Furthermore, the addition of these fatty acids to the culture medium increased energy production by rat-CMs and hiPSC-CMs and enhanced the contractility of myocardial tissue generated from hiPSC-CMs. These findings suggest that the addition of fatty acids to the culture medium stimulates aerobic energy production by cardiomyocytes through β-oxidation. Since cardiomyocytes cultured in standard media rely primarily on anaerobic glucose metabolism and remain in an immature state, further research is merited to establish whether the addition of fatty acids to the culture medium would improve the energy-producing capacity and maturity of hiPSC-CMs and cardiac tissue constructed from these cells. It is possible that optimizing the metabolism of cultured cardiomyocytes, which require high energy production to sustain their contractile function, will improve the properties of hiPSC-CM-derived tissue, allowing it to be better utilized for disease modeling, drug screening and regenerative therapies for heart failure.
UNASSIGNED:基于对大鼠原代心肌细胞(rat-CM)脂肪酸消耗的分析,开发了一种含脂肪酸的培养基,和该培养基对三磷酸腺苷(ATP)生产的影响通过生物发光成像的萤光素酶表达的大鼠CMs进行了研究。基于对猪心脏和hiPSC-CM脂肪酸利用的分析,进一步调整培养基的脂肪酸含量,进行氧消耗分析以探索含脂肪酸的培养基是否诱导hiPSC-CM从无氧代谢转变为有氧代谢。此外,评价培养基对hiPSC-CM来源的组织产生的收缩力的影响。
未经证实:大鼠血清,人血清和猪血浆含有相似类型的脂肪酸(油酸,硬脂酸,亚油酸,棕榈酸和花生四烯酸)。在大鼠-CM之间消耗的脂肪酸类型也相似,hiPSC-CM和猪心脏。向培养基中添加脂肪酸增加了表达荧光素酶的大鼠CMs的生物发光(ATP水平的间接测量),HiPSC-CM的耗氧量,和由hiPSC-CM构建的心脏组织产生的收缩力。
UNASSIGNED:hiPSC-CM代谢与大鼠CM和猪心脏消耗的脂肪酸相似。此外,在培养基中添加这些脂肪酸增加了大鼠-CM和hiPSC-CM的能量产生,并增强了hiPSC-CM产生的心肌组织的收缩性。这些发现表明,在培养基中添加脂肪酸通过β-氧化刺激心肌细胞的有氧能量产生。由于在标准培养基中培养的心肌细胞主要依赖于厌氧葡萄糖代谢并保持在未成熟状态,值得进一步研究以确定在培养基中添加脂肪酸是否会提高由这些细胞构建的hiPSC-CM和心脏组织的能量产生能力和成熟度。有可能优化培养心肌细胞的代谢,这需要高能量生产来维持它们的收缩功能,将改善hiPSC-CM衍生组织的性质,让它更好地用于疾病建模,心力衰竭的药物筛查和再生治疗。