Autophagy and Reactive Oxygen Species in Megakaryopoiesis and Platelet Production.

Megakaryocytes (MKs), which are differentiated from megakaryocytic-erythrocytic progenitors, generate platelets (PLTs) by expanding and branching their cellular fragments under the influence of cytokines and intercellular mechanisms such as autophagy and release of reactive oxygen species (ROS) in the bone marrow. Autophagy is a self-destructive process that plays a significant role in cell growth and energy maintenance of the cells. In contrast, ROS are toxic products of cellular metabolism that are harmful to human stem cells but have a crucial role in determining lineage commitment at the common myeloid progenitor stage and deriving further maturation progression toward MKs and PLTs production, with an interconnected relationship in the onset and deriving of autophagy. This review summarizes and discusses what has been discovered about the current state of knowledge regarding autophagy effects on MK differentiation, ROS effects on megakaryopoiesis (MKp), and the relationship between these molecules and autophagy initiation. Furthermore, in vitro applications of controlling these external factors on MKp are reviewed according to pertinent studies. Utilizing these regulatory mechanisms supports an improved design of in vitro MKp for introducing artificial PLT sources and might be beneficial in creating novel treatments of PLT-related coagulation disorders.