Trieschmann Jan, Bettin Daniel, Haustein Moritz, Köster Annette, Molcanyi Marek, Halbach Marcel, Hanna Mira, Fouad Mariam, Brockmeier Konrad, Hescheler Jürgen, Pfannkuche Kurt, Hannes Tobias
Department of Paediatric Cardiology, Heart Centre Cologne, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany; Institute for Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, 50931 Cologne, Germany.
Department of Paediatrics, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany.
Stem Cells Int. 2016;2016:2936126. doi: 10.1155/2016/2936126. Epub 2016 Jan 5.
Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 ± 15.2% versus 9.3 ± 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 ± 1.7 mV versus 65.1 ± 1.5 mV, V max: 7.0 ± 1.0 V/s versus 36.5 ± 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 ± 1.0 ms versus 16.8 ± 1.9 ms, p < 0.001; APD90: 52.2 ± 1.5 ms versus 43.3 ± 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology.
干细胞衍生的心肌细胞移植是心肌梗死后最有前景的治疗方法之一，因为内源性修复机制几乎无法逆转心肌细胞的损失。在心肌瘢痕中，移植的心肌细胞将直接与心脏成纤维细胞接触。虽然已有充分文献记载同一发育阶段的心脏成纤维细胞如何调节新生心肌细胞的电生理学，但尚不清楚成年心脏成纤维细胞（aCFs）如何影响胚胎干细胞衍生的心肌细胞（ESC-CMs）的功能。为了研究aCFs对ESC-CM电生理学的影响，我们对小鼠aCF-ESC-CM共培养物进行了细胞外和细胞内记录。我们观察到，与间充质干细胞共培养相比，aCF-ESC-CM共培养中的自发搏动行为高度不规则（峰间间期变异系数：40.5±15.2%对9.3±2.0%，p = 0.008），动作电位幅度和最大上升速度（V max）降低（幅度：52.3±1.7 mV对65.1±1.5 mV，V max：7.0±1.0 V/s对36.5±5.3 V/s），而动作电位持续时间（APD）延长（APD50：25.6±1.0 ms对16.8±1.9 ms，p < 0.001；APD90：52.2±1.5 ms对43.3±3.3 ms，p < 0.01）。aCF条件培养基也可诱导类似变化。我们得出结论，aCFs的存在会改变自律性，并诱导ESC-CM电生理学发生潜在的促心律失常变化。
