Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad-mesonephros–derived stromal cell lines

M Xu, K Tsuji, T Ueda, Y Mukouyama… - Blood, The Journal …, 1998 - ashpublications.org
M Xu, K Tsuji, T Ueda, Y Mukouyama, T Hara, FC Yang, Y Ebihara, S Matsuoka, A Manabe
Blood, The Journal of the American Society of Hematology, 1998ashpublications.org
We report here on a novel stromal cell line, AGM-S3, derived from the aorta-gonad-
mesonephros (AGM) region of a 10.5 days postcoitum (dpc) mouse embryo. The AGM-S3
cells promoted production of hematopoietic progenitors and day-12 spleen colony-forming
cells from Lin− c-Kit+ Sca-1+ murine primitive hematopoietic cells. They also supported for 6
weeks generation of human multipotential progenitors from cord blood CD34+ CD38−
primitive hematopoietic cells. Human long-term repopulating hematopoietic stem cells (LTR …
Abstract
We report here on a novel stromal cell line, AGM-S3, derived from the aorta-gonad-mesonephros (AGM) region of a 10.5 days postcoitum (dpc) mouse embryo. The AGM-S3 cells promoted production of hematopoietic progenitors and day-12 spleen colony-forming cells from Linc-Kit+Sca-1+ murine primitive hematopoietic cells. They also supported for 6 weeks generation of human multipotential progenitors from cord blood CD34+CD38 primitive hematopoietic cells. Human long-term repopulating hematopoietic stem cells (LTR-HSC) with the potential to reconstitute hematopoiesis in NOD/SCID mice were maintained on AGM-S3 cells for at least 4 weeks. Flow cytometric analysis showed that CD13, vascular cellular adhesion molecule-1, and Sca-1 were expressed on AGM-S3 cells. Because stem cell factor, interleukin-6 (IL-6), and oncostatin M, but not IL-3, IL-11, leukemia- inhibitory factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, thrombopoietin, and Flk2 ligand were detected in reverse transcription-polymerase chain reaction analysis of AGM-S3 cells, the cells seem to express species-cross reactive molecule(s) other than the cytokines examined and which act on primitive hematopoietic progenitor/stem cells. This cell line is expected to elucidate molecular mechanisms regulating early hematopoiesis and pave the way for developing strategies for expansion of human transplantable HSC.
© 1998 by The American Society of Hematology.
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