Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor with neuroprotective properties. TPO is most prominent in postnatal brain, whereas EPO is abundant in embryonic brain and decreases postnatally. Upon hypoxia, EPO and its receptor are rapidly reexpressed, whereas neuronal TPO and its receptor are down-regulated. Unexpectedly, TPO is strongly proapoptotic in the brain, causing death of newly generated neurons through the Ras-extracellular signal-regulated kinase 1͞2 pathway. This effect is not only inhibited by EPO but also by neurotrophins. We suggest that the proapoptotic function of TPO helps to select for neurons that have acquired targetderived neurotrophic support.astrocytes ͉ erythropoietin ͉ neurons ͉ differentiation ͉ development I n the hematopoietic system, survival, proliferation, and differentiation of cells are regulated by a plethora of growth factors (1-4). The effect of erythropoietin (EPO) on the generation of red blood cells is well known. The hematopoietic growth factor thrombopoietin (TPO) stimulates megakaryopoiesis and thrombocyte formation (1-3, 5, 6). During hematopoiesis, EPO and TPO can interact in a synergistic and an antagonistic fashion (1-3, 7).EPO and TPO exhibit significant homology in their receptorbinding domain (20% identity and 25% similarity). Likewise, they bind to receptors, erythropoietin receptor (EPOR) and thrombopoietin receptor (TPOR), respectively, that belong to the same cytokine receptor superfamily (1)(2)(3)(8)(9)(10). Previous studies reported a neurotrophin-like motif in the N-terminal receptor binding region of the TPO molecule, with conflicting data about the presence of TPO in the brain (5,6,(11)(12)(13).For EPO, it is well established that the gene is expressed in the embryonic CNS. EPO has a marked effect as a survival factor for neurons and their progenitors (14, 15), presumably to overcome phases of physiological hypoxia (16, 17). The widespread but rather ''unspecific'' neuroprotective potential of EPO is regained in the adult CNS upon distress or injury. This finding has been confirmed in rodent models of cerebral ischemia (18-23), brain trauma (18), and neurodegenerative disease (18), as well as in a clinical study with stroke patients (24).Here we show that TPO plays a previously unrecognized proapoptotic role in the brain. Materials and MethodsAll experiments were approved by and conducted in accordance with the regulations of the local Animal Care and Use Committee. For detailed information on all methods see Supporting Materials and Methods, which is published as supporting information on the PNAS web site.Cell Culture. Primary hippocampal neuronal cultures were prepared from newborn Wistar-Imamichi rats, cultured under serum-free conditions (25, 26), and used for experiments after five days (purity: Ͼ95% neurons). Neuronal cell number and viability was assessed by try...

Myeloproliferative virus, derived from Moloney sarcoma virus, causes erythroleukemia and myeloid leukemia in adult mice. This virus is also capable of fibroblast transfornation in vitro. The virus consists of two separable biological entities which have been cloned. The helper virus component caused no visible changes in adult mice, whereas the defective virus induced both spleen focus formation and a large increase in erythroid precursor cells but retained the sarcoma virus property of transforming fibroblasts in vitro. Thus, myeloproliferative virus is the first murine sarcoma virus which induces erythroleukemia in adult animals.

LVL results in a higher yield of CD34+ cells and colony-forming units-granulocyte-macrophage than NVL, but only in patients with breast cancer and with high numbers of CD34+ cells in the peripheral blood before leukapheresis.

A good correlation between the variables used for characterization of peripheral blood progenitor cells--the number of CD34+ cells and the number of CFU-GM--was observed. Viability assessment by trypan blue exclusion does not seem to be a substitute for assays evaluating in vitro proliferative capacity.

Progenitor cells with differentiation capacity along multiple mesengenic lineages are attractive tools for numerous purposes in regenerative medicine. Such mesengenic progenitor cells have been isolated from adult mammalian bone marrow, and we here report placental tissue as an alternative source for these cells. By means of dissection/proteinase digestion techniques, high numbers of viable mononuclear cells were harvested from human placenta at term, and a mesenchymal cell population with characteristic expression of CD9, CD29, and CD73 was obtained in culture. The in vitro growth behavior of such placenta-derived mesengenic cells was similar to that of human bone marrow mesengenic progenitor cells. After in vitro propagation for more than three passages the cells were exclusively of maternal origin. Differentiation experiments showed differentiation potential along osteogenic, chondrogenic, adipogenic, and myogenic lineages. In conclusion, we propose human term placenta as an easily accessible, ample source of multipotent mesengenic progenitor cells.