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

Ming Jiang Xu, Kohichiro Tsuji, Takahiro Ueda, Yoh Suke Mukouyama, Takahiko Hara, Feng Chun Yang, Yasuhiro Ebihara, Sahoko Matsuoka, Atsushi Manabe, Akira Kikuchi, Mamoru Ito, Atsushi Miyajima, Tatsutoshi Nakahata

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132 Scopus citations

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 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-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.

Original languageEnglish (US)
Pages (from-to)2032-2040
Number of pages9
JournalBlood
Volume92
Issue number6
StatePublished - Sep 15 1998

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Xu, M. J., Tsuji, K., Ueda, T., Mukouyama, Y. S., Hara, T., Yang, F. C., Ebihara, Y., Matsuoka, S., Manabe, A., Kikuchi, A., Ito, M., Miyajima, A., & Nakahata, T. (1998). Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad-mesonephros-derived stromal cell lines. Blood, 92(6), 2032-2040.