RESUMO
The ex vivo maintenance and expansion of hematopoietic stem cells and early progenitors is necessary for the successful treatment of hematopoietic and immune diseases. Multiple attempts to improve the expansion of hematopoietic stem cells (HSCs) by their cultivation in the presence of growth factor cocktails have so far failed. Novel approaches aimed at conserving the earliest precursors in their undifferentiated state are needed. These approaches should take into account local regulatory factors that are present in the HSC microenvironment and the three-dimensional architecture of their niche. In the present study, we compared the effects of two Notch ligands, i.e., Jagged1 and DLL1, on murine and human hematopoiesis in vitro. Our observations indicate that the stromal expression of Notch ligands increases the production of both the total and phenotypically early murine and human hematopoietic cells in the co-culture. On one hand, this study demonstrates the similarity of effects of stromal expression of Notch ligands on murine and human hematopoiesis in vitro. On the other hand, our study revealed a number of cell type and ligand-specific variations that are systematically described below. It seems that the effects of SCF cytokine addition on murine hematopoiesis in vitro depend on the stromal context and are oppositely directed for Jagged1 and DLL1.
Assuntos
Hematopoese/fisiologia , Células-Tronco Hematopoéticas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1/metabolismo , Animais , Proteínas de Ligação ao Cálcio , Células-Tronco Hematopoéticas/citologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteína Jagged-1/genética , Camundongos , Células NIH 3T3 , Fator de Células-Tronco/genética , Fator de Células-Tronco/metabolismo , Células Estromais/citologia , Células Estromais/metabolismoRESUMO
Comparison of mesenchymal stromal cells of embryonic and adult rat spleen showed that splenic cells from 20-day rat fetuses exhibit the capacity for clonal growth, express surface antigens CD73, CD90, and CD106, and have weak osteogenic and adipogenic potencies, while splenic cells from adult animals are characterized by lower cloning efficiency, rapid decrease of proliferative activity during passaging, the absence of CD73 and CD90 expression, and are incapable of osteogenesis The observed changes are probably related to extinction of myelopoiesis in the spleen during the postnatal ontogeny.
