Do megakaryocytes contribute to organ fibrosis?

Megakaryocytes, the platelet precursors, have been known to populate tissues other than the bone marrow, most prominently the lung, but also the liver and spleen. Work in myeloproliferative neoplasms has established that dysplastic megakaryocytes are central organisers of the fibrosis in the bone marrow. In this commentary, we frame a hypothesis-gathering question as to whether megakaryocytes might analogously act as context-dependent contributors to organ fibrosis outside the marrow. In the lung, studies have identified resident/trafficking megakaryocytes with inflammatory properties, while in the liver, megakaryocytes-rich extramedullary foci often co-localise with periportal and perisinusoidal fibrosis. Approved agents for idiopathic pulmonary fibrosis act on broad growth-factor pathways across multiple cell types that may overlapwith the megakaryocytes/platelet secretome. It is thus possible that megakaryocytes may play a contributory role in organ fibrosis. We acknowledge that these observations are associative and preclinical, and that established epithelial-mesenchymal mechanisms remain central in organ fibrosis. We therefore do not assert that megakaryocytes are contributors of organ fibrosis. Rather, we pose this as a testable question prompted by converging yet incomplete evidence.