On the other hand, Naveiras et al. reported the BM adipocytes as negative regulators of the hematopoietic microenvironment using lipoatrophic A-ZIP/F1 ��fatless�� mice. In the study, transplantation of normal BM cells in lethally irradiated A-ZIP/F1 mice lacking adipogenesis showed enhanced hematopoietic recovery compared with wild-type recipient mice, indicating that adipocytes in fatty Semaxanib VEGFR/PDGFR inhibitor marrow hinder hematopoietic progenitor expansion. In humans, it is also known that fatty marrow gradually predominates with age. It should be noted that some myeloid diseases such as aplastic anemia displaying anemia, and/or pancytopenia are accompanied by severe fatty marrow. These reports strongly suggest that the cellularity of adipocytes, osteoblasts and other mesenchymal stromal cells in the BM is critical for an adequate hematopoietic microenvironment. As these cells could be derived from MSC in the BM, the factor that regulate their balance would be a novel therapeutic target for impaired hematopoiesis in fatty marrow and for enhancing hematopoietic engraftment after BM transplantation. OSM is a member of the interleukin -6 family of cytokines and has various unique biological activities e.g. hematopoiesis, hepatogenesis and adipogenesis, which are not shared by the other family members. Murine OSM is expressed in the aorta-gonad-mesonephros region, where long-term repopulating HSC arise, and OSM stimulates the expansion of multipotential hematopoietic progenitors in the primary culture of AGM. While OSM also expanded hematopoietic stem/progenitor cells in co-cultures of AGM and fetal liver cells, it induced the differentiation of fetal hepatocytes in vitro. Despite its strong and unique activities in vitro, the genetic ablation of either OSM or its receptor in mice unexpectedly showed no severe defects during development. In contrast, these adult knockout mice displayed anemic and thrombocytopenic phenotype although the symptoms were relatively mild. Colony-forming unit assays showed that the number of hematopoietic progenitors in BM was LY294002 significantly reduced in KO mice compared to wild-type mice, whereas that in spleen was increased. Additionally, the number of hematopoietic progenitors in peripheral blood was increased in OSM KO mice, indicating the mobilization of HSPC from the BM into the circulation. These reports suggest the possibility that the BM niche harboring HSPC is impaired in OSM KO mice. OSM was shown to inhibit the adipocytic differentiation of 3T3L1 cells, a preadipocyte cell line, mouse embryonic fibroblasts, adipose tissuederived MSC and BM MSC. Considering the BM adipocytes as a negative regulator of the hematopoietic microenvironment, the lack of inhibitory effect of OSM on adipogenesis from MSC may account for the reduced hematopoietic activity in OSM KO BM. However, the causal linkage between these two original findings has remained uninvestigated. Although Walker et al. reported that marrow adipocyte volume was increased in 12-week-old OSMR KO mice, the role of OSM in the BM microenvironment for hematopoiesis has not been elucidated.