Regulation of megakaryocytopoiesis

Megakaryocytopoiesis is the cellular developmental process prior to the release of platelets into the circulation. Regulation of megakaryocytopoiesis is a complex phenomenon that begins with commitment of hematopoietic stem cells to the replication and maturation of progenitor cells through endomitosis and megakaryocyte differentiation [1-4]. Platelet production is determined by the number and size of megakaryocytes in the marrow and may be regulated at two levels: at early stages of cell proliferation resulting in increased megakaryocyte numbers, and at later stages by endoreplication which increases DNA content and the size of megakaryocytes [5]. The mature megakaryocyte is a large polyploid cell with a highly defined invaginated membrane (demarcation membrane) and contains the membrane molecules necessary for platelet function [6-9]. Platelet shedding appears to occur by fragmentation of the cytoplasm of the megakaryocyte. Platelet release is thought to occur via transendothelial processes projecting into the vascular compartment [10, 11], although several studies indicate that megakaryocytes lodged in the lungs are capable of platelet formation [12-17]. The factors stimulating megakaryocytopoiesis in the lung have not been well characterized. In the past, the study of megakaryocyte development in vivo and in vitro was hampered by the rarity of megakaryocytes in the bone marrow, the poorly defined cell populations, and inadequate assays. These prior studies of megakaryocyte development have been discussed in the recent past by R. Hoffman [1], N. Williams [3], and M. W. Long [2]. An attempt will be made in this review to highlight and synthesize various new concepts of regulation of megakaryocytopoiesis.