Redox Regulation of Megakaryocyte Differentiation and Platelet Biogenesis

Pathological accumulation of reactive oxygen species (ROS) is implicated in several diseases, including cancer, cardiovascular diseases, and aging. However, ROS play essential roles in cellular functions, including proliferation, differentiation, and immune responses, at physiological levels. In megakaryocytes, the cells responsible for producing platelets, ROS exert context-dependent effects, either promoting or impairing maturation depending on developmental stage and subcellular localization. In this review, we summarize current evidence demonstrating that balanced ROS signaling is required throughout megakaryocyte development. Further, we discuss how the source and timing of ROS generation determine their distinct stage-specific functions, and the role of ROS dysregulation in defective platelet production in conditions such as aging, inflammation, and hematopoietic stress. We further highlight the importance of redox regulation for efficient in vitro platelet manufacturing. Although stem cell-derived platelets hold great promise for addressing global platelet shortages, current systems produce significantly fewer platelets than are found naturally. We propose that limited understanding and poor control of ROS dynamics contribute to limited platelet yield and quality. By viewing ROS as tunable biological signals rather than solely as harmful byproducts, we emphasize redox modulation as a practical and actionable approach to enhance platelet biogenesis and support the development of next-generation platelet therapies.