Reactive oxygen species (ROS) have been implicated in mechanisms of heart development and regenerative therapies such as the use of pluripotent stem cells. The roles of ROS mediating cell fate are dependent on the intensity of stimuli, cellular context, and metabolic status. ROS mainly act through several targets (such as kinases and transcription factors) and have diverse roles in different stages of cardiac differentiation, proliferation, and maturation. Therefore, further detailed investigation and characterization of redox signaling will help the understanding of the molecular mechanisms of ROS during different cellular processes and enable the design of targeted strategies to foster cardiac regeneration and functional recovery. In this review, we focus on the roles of ROS in cardiac differentiation as well as transdifferentiation (direct reprogramming). The potential mechanisms are discussed in regard to ROS generation pathways and regulation of downstream targets. Further methodological optimization is required for translational research in order to robustly enhance the generation efficiency of cardiac myocytes through metabolic modulations. Additionally, we highlight the deleterious effect of the host’s ROS on graft (donor) cells in a paracrine manner during stem cell-based implantation. This knowledge is important for the development of antioxidant strategies to enhance cell survival and engraftment of tissue engineering-based technologies. Thus, proper timing and level of ROS generation after a myocardial injury need to be tailored to ensure the maximal efficacy of regenerative therapies and avoid undesired damage.

中文翻译：

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活性氧在心脏分化，重编程和再生疗法中的作用。

活性氧（ROS）与心脏发育和再生疗法（如多能干细胞的使用）有关。ROS介导细胞命运的作用取决于刺激强度，细胞背景和代谢状态。ROS主要通过多种靶标（例如激酶和转录因子）起作用，并且在心脏分化，增殖和成熟的不同阶段具有不同的作用。因此，对氧化还原信号的进一步详细研究和表征将有助于了解不同细胞过程中ROS的分子机制，并能够设计靶向策略以促进心脏再生和功能恢复。在这篇评论中 我们专注于ROS在心脏分化以及转分化（直接重编程）中的作用。讨论了有关ROS生成途径和下游靶标调控的潜在机制。翻译研究需要进一步的方法学优化，以通过代谢调节来稳健地提高心肌细胞的生成效率。此外，在基于干细胞的植入过程中，我们以旁分泌方式突出了宿主ROS对移植（供体）细胞的有害作用。该知识对于开发抗氧化剂策略以提高细胞存活率和基于组织工程技术的植入至关重要。从而，