RESUMO
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 1/2 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 target-derived neurotrophic support.
Assuntos
Apoptose , Química Encefálica , Encéfalo/citologia , Eritropoetina/fisiologia , Trombopoetina/fisiologia , Animais , Encéfalo/metabolismo , Regulação da Expressão Gênica , Fatores de Crescimento de Células Hematopoéticas/fisiologia , Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/farmacologia , Neurônios/citologia , Neurônios/metabolismo , Prosencéfalo/química , Prosencéfalo/citologia , Rombencéfalo/química , Rombencéfalo/citologiaRESUMO
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.