Role of thrombopoietin in hematopoietic stem cell and progenitor regulation

Thrombopoietin performs an essential role during hematopoiesis by regulating the expansion and maturation of megakaryocytes. In keeping with this function, megakaryocytes, platelets, and their precursors all express the thrombopoietin receptor, Mpl, on their cell surface. However, Mpl is also expressed on primitive, pluripotent hematopoietic progenitors and plays an important role in the regulation of lineages other than megakaryocytes as well as primitive progenitors. Recently, the ability of thrombopoietin to maintain and expand repopulating stem cells has been demonstrated. Thus, thrombopoietin is unique among the hematopoietic cytokines because it is necessary both for terminal maturation and regulation of lineage-specific megakaryocytes and also for maintenance of the most primitive hematopoietic stem cells. Many new strategies are evolving to exploit the activity of thrombopoietin on primitive progenitors. This may lead to faster hematopoietic recovery from marrow-suppressive therapy, effective methods of ex vivo expansion of hematopoietic stem cells, and retroviral transduction of stem cells to facilitate gene therapy.