Thrombopoietin and hematopoietic stem cell development.

Thrombopoietin, the long sought primary regulator of thrombopoiesis, was cloned four years ago. In addition to its fulfilling most, if not all, of the expected biological activities relating to megakaryocyte and platelet development, the availability of the recombinant hormone and reagents to characterize its receptor have allowed detailed investigation of additional biological activities. In cultures of purified populations of candidate stem cells, thrombopoietin supports the survival, and augments the proliferation of hematopoietic stem cells when present together with interleukin-3 or steel factor. The progeny of such cultures are not skewed in their developmental potential; colony-forming cells of all lineages arise from thrombopoietin-stimulated stem cells. Evidence for an important effect of thrombopoietin on stem cell physiology in vivo are equally compelling. Genetic elimination of thrombopoietin or its receptor leads to a profound reduction not only of megakaryocytes and platelets, but also of committed myeloid progenitors of all types, primitive progenitors and hematopoietic stem cells. When administered to animals, thrombopoietin profoundly stimulates thrombopoiesis and enhances the number of hematopoietic progenitor cells of all lineages, and when used in most animal models of myelosuppressive therapy, accelerates the recovery of platelet, erythrocyte and leukocyte production. Thus, thrombopoietin appears to be more than a lineage-restricted growth factor.