Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies
Jialiang Liang1, Min Wu1, Chen Chen1
1Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
Abstract:
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.
Insights
Reactive oxygen species (ROS) are crucial for heart development and regeneration. Understanding ROS signaling is key to improving cardiac repair strategies and enhancing stem cell therapy efficacy.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Redox Signaling
Background:
- Reactive oxygen species (ROS) play complex roles in cardiac development and regenerative medicine.
- ROS influence cell fate decisions during cardiac differentiation, proliferation, and maturation.
- The precise impact of ROS depends on stimulus intensity, cellular context, and metabolic state.
Purpose of the Study:
- To review the multifaceted roles of ROS in cardiac differentiation and direct reprogramming.
- To elucidate the molecular mechanisms underlying ROS generation and downstream target regulation.
- To highlight strategies for optimizing ROS-mediated cardiac regeneration and stem cell therapy.
Main Methods:
- Literature review focusing on ROS in cardiac differentiation and transdifferentiation.
- Analysis of ROS generation pathways and their regulation of cellular targets.
- Discussion of methodological needs for translational research in cardiac regeneration.
Main Results:
- ROS signaling is critical but context-dependent in cardiac cell processes.
- Understanding ROS mechanisms can guide targeted strategies for cardiac repair.
- Host ROS can negatively impact transplanted cells, necessitating antioxidant interventions.
Conclusions:
- Tailoring ROS levels and timing is essential for effective cardiac regenerative therapies.
- Optimizing metabolic pathways can enhance cardiac myocyte generation efficiency.
- Developing antioxidant strategies is crucial for improving stem cell survival and engraftment in tissue engineering.
