Generation of cardiomyocytes from human pluripotent stem cells (hPSCs) is of high interest for disease modelling and regenerative medicine. hPSCs can provide an unlimited source of patient-specific cardiomyocytes that are otherwise difficult to obtain from individuals. Moreover, the low proliferation rate of adult cardiomyocytes and low viability limits the quantity of study material. Most protocols for the differentiation of cardiomyocytes from hPSCs are based on the temporal modulation of the Wnt pathway. However, during the initial stage of GSK-3 inhibition, a substantial number of cells are lost due to detachment. In this study, we aimed to increase the efficiency of generating cardiomyocytes from hPSCs. We identified cell death as a detrimental factor during this initial stage of cardiomyocyte differentiation. Through pharmacological targeting of different types of cell death, we discovered that ferroptosis was the main cell death type during the first 48 h of the differentiation procedure. Inhibiting ferroptosis using ferrostatin-1 during cardiomyocyte differentiation resulted in increased robustness and cell yield.

中文翻译：

---

通过靶向铁死亡改善人类多能干细胞的心脏分化

从人类多能干细胞（hPSC）生成心肌细胞对于疾病建模和再生医学具有很高的意义。hPSC 可以提供无限的患者特异性心肌细胞来源，而这些细胞很难从个体中获得。此外，成体心肌细胞的低增殖率和低活力限制了研究材料的数量。大多数从 hPSC 中分化心肌细胞的方案都是基于 Wnt 通路的时间调节。然而，在 GSK-3 抑制的初始阶段，大量细胞因脱离而损失。在这项研究中，我们的目标是提高 hPSC 生成心肌细胞的效率。我们确定细胞死亡是心肌细胞分化初始阶段的有害因素。通过针对不同类型细胞死亡的药理学靶向，我们发现铁死亡是分化过程的前 48 小时内主要的细胞死亡类型。在心肌细胞分化过程中使用 Ferrostatin-1 抑制铁死亡可提高稳定性和细胞产量。