Document Detail


Flk1+ cells derived from mouse embryonic stem cells reconstitute hematopoiesis in vivo in SCID mice.
MedLine Citation:
PMID:  12482507     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Embryonic stem (ES) cells are pluripotent and can differentiate into any cell type, including the hematopoietic lineage. We examined whether hematopoietic progenitor cells derived from ES cells reconstitute hematopoiesis in irradiated SCID mice. MATERIALS AND METHODS: ES cells (E14.1, H2K(b)) were cultured for 4 days in semisolid medium containing methylcellulose. Irradiated SCID mice were used as recipients of hematopoietic progenitor cells. Cell surface antigen expression was analyzed by flow cytometry. The spleens of the recipient mice were studied by hematoxylin and eosin staining and immunohistochemical staining. RESULTS: After cell culture of ES cells in methylcellulose for 4 days, the cells expressing Flk1 (VEGF receptor 2), a tentative marker of hemangioblasts, were increased, whereas cells expressing CD31 (PECAM-1) and E-cadherin (nonmesodermal adhesion molecule) were dramatically reduced. Flk1+ cells expressed c-kit predominantly. Circulating leukocytes and thrombocytes were increased in irradiated SCID (H2K(d)) mice transplanted with ES cell-derived Flk1+ cells compared with vehicle-injected control mice. H2K(b+) and VE-cadherin(+) vascular endothelial cells were prominent in spleens of the recipient mice. Flow cytometric analysis demonstrated that H2K(b+) cells were increased in the bone marrow of recipient mice. In addition, Flk1+ cells accompanying enhanced c-kit expression preferentially repopulated in the bone marrow, and leukopoiesis and thrombopoiesis of the recipient mice were evident. CONCLUSION: The Flk1+ hematopoietic cells derived from ES cells reconstitute hematopoiesis in vivo and may become an alternative donor source for bone marrow transplantation.
Authors:
Tsukasa Miyagi; Mitsuhiro Takeno; Hiroko Nagafuchi; Masatomo Takahashi; Noboru Suzuki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental hematology     Volume:  30     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-16     Completed Date:  2003-04-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1444-53     Citation Subset:  IM    
Affiliation:
Departments of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Surface / analysis
Cadherins / genetics
Cell Culture Techniques / methods
Cell Differentiation
Embryo, Mammalian / cytology
Female
Hematopoiesis*
Hematopoietic Stem Cell Transplantation / adverse effects,  methods*
Hematopoietic Stem Cells / cytology*
Methylcellulose
Mice
Mice, SCID
Pluripotent Stem Cells / cytology*
Spleen / cytology
Vascular Endothelial Growth Factor Receptor-2 / physiology*
Chemical
Reg. No./Substance:
0/Antigens, Surface; 0/Cadherins; 9004-67-5/Methylcellulose; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2

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