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Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2032-2040
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, and
Tatsutoshi Nakahata
From the Department of Clinical Oncology, The Institute of Medical
Science, and the Institute of Molecular and Cellular Bioscience, The
University of Tokyo, Tokyo, Japan; and the Central Institute for
Experimental Animals, Kawasaki, Japan.
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.
© 1998 by The American Society of Hematology.
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