In today’s session, Dr. Joseph Italiano described advancements in the understanding of platelet function made by his laboratory and explains how this knowledge has been used to leverage the production of platelets in-vitro.
Italiano uses new technology, including machine learning, to study the biological processes involved in platelet production. Machine learning employs algorithms that can accurately segment megakaryocyte and proplatelet structures to study the mechanisms of platelet production and dysfunction in diseases such as drug-induced thrombocytopenia and other conditions.
Italiano discussed internal factors (also referred to as cytosolic factors) that trigger proplatelet initiation. To identify this internal driver, he asked himself “Do megakaryocytes undergoing platelet formation contain a cytosolic factor that promotes platelet formation?” To answer this question his lab injected cytosol from proplatelet-producing megakaryocytes into megakaryocytes. Upon doing so, these cells began producing platelets as compared to sham controls. So, the next logical question was “what is this cytosolic factor and what does it regulate?
When discussing the master regulator of proplatelet initiation, Italiano suggests that the centrosome may play that central role. Centrosomes may help initiate proplatelet formation by transporting microtubules towards the cell surface. It is further postulated that centrosome related proteins are dynamically regulated during proplatelet formation.
Unravelling key regulators of proplatelet formation has direct relevance in the field of transfusion medicine and the in vitro production of platelets for clinical applications. Here, the use of pluripotent stem cells, under the influence of cytokines such as thrombopoietin, gives scientists the ability to create functional megakaryocytes. The real barrier in this field to date has been the ability to trigger these megakaryocytes cells to make platelets. Finding the master regulator of proplatelet formation may therefore enable this process and the long-term goal to produce platelets in-vitro platelets. According to Dr. Italiano, “this advance has the ability to revolutionize platelet transfusion medicine.”