Platelets are small, disc-shaped cell fragments in the blood that are essential to stop bleeding and to initiate blood clotting after injury. Platelet transfusions in patients with severe trauma or medical conditions, including bone marrow disease, leukemia, or sepsis, can be lifesaving. Despite being a standard clinical practice, platelet transfusions face issues related to the availability of blood donations from which platelets are isolated, the relatively short shelf life of purified platelets, and the risk of an immune response in patients receiving platelets from unmatched donors.

A potential solution to this has been proposed by the team of Koji Eto at the Center for iPS Cell Research and Application at Kyoto University, Japan, who invented a method for manufacturing platelet-producing cells, megakaryocytes, from stem cells. Via genetic engineering, Koji's team first made so-called induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells and then converted them into megakaryocytes in the lab. Platelets can then be harvested from the megakaryocyte cultures and given back to the same patient, thereby avoiding immune rejection.

Although this strategy, in theory, provides an unlimited supply of patient-derived platelets, some impediments towards industrial large-scale production remain, most notably variable efficiency of platelet production from megakaryocytes across different patients and a decrease in productivity over time.

In their work published today in Stem Cell Reports, Eto's team addresses these issues by showing that megakaryocyte growth is directly linked to platelet production and is controlled by the protein KAT7, which acts as a "molecular switch." While megakaryocytes with high KAT7 levels divide fast and make high amounts of platelets, megakaryocytes with low KAT7 levels switch behavior-they stop multiplying, accumulate DNA damage, and produce more inflammatory proteins-while at the same time ceasing platelet production.

This work demonstrates that maintaining high cellular KAT7 levels is essential for consistently high platelet production from stem cell-derived megakaryocytes. Monitoring KAT7 levels can potentially be used for quality control during clinical-scale production and thus be leveraged to ensure efficient and consistent platelet manufacturing across patients.