Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad-mesonephros-derived stromal cell lines.
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.
Xu
M J
MJ
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.
Tsuji
K
K
Ueda
T
T
Mukouyama
Y S
YS
Hara
T
T
Yang
F C
FC
Ebihara
Y
Y
Matsuoka
S
S
Manabe
A
A
Kikuchi
A
A
Ito
M
M
Miyajima
A
A
Nakahata
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001011:Aorta / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D006066:Gonads / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000096:biosynthesis; D008650:Mesonephros / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009244:NAD+ Nucleosidase / Q000032:analysis; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D017077:Culture Media, Conditioned; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1