Stem Cells
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First published online December 8, 2005
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2005-0457v1
24/4/850    most recent
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Submitted on September 19, 2005
Accepted on November 16, 2005

Original Article

Murine Embryonic Stem Cells Secrete Cytokines/Growth Modulators that Enhance Cell Survival/Anti-Apoptosis and Stimulate Colony Formation of Murine Hematopoietic Progenitor Cells

Ying Guo 1, Barbara Graham-Evans 1, Hal E. Broxmeyer 1*

1 Department of Microbiology/Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana

* To whom correspondence should be addressed. E-mail: hbroxmey{at}iupui.edu.


  Abstract

SDF-1/CXCL12, released by murine embryonic stem (ES) cells, enhances survival, chemotaxis, and hematopoietic differentiation of murine ES cells. Conditioned medium (CM) from murine ES cells growing in the presence of LIF was generated while the ES cells were in an undifferentiated Oct-4 expressing state. ES cell CM enhanced survival of normal murine bone marrow myeloid progenitors (CFU-GM) subjected to delayed growth factor addition in vitro and decreased apoptosis of murine bone marrow c-kit+lin- cells. ES CM contained IL-1{alpha}, IL-10, IL-11, M-CSF, OSM, SCF, VEGF, as well as a number of chemokines and other proteins, some of which are known to enhance survival/antiapoptosis of progenitors. Irradiation of ES cells enhanced release of some proteins and decreased release of others. IL-6, FGF-9, and TNF-{alpha}, not detected prior to irradiation was found after ES cells were irradiated. ES cell CM also stimulated CFUGM colony formation. Thus, undifferentiated murine ES cells growing in the presence of LIF produce/release a number of biologically active interleukins, CSFs, chemokines, and other growth modulatory proteins, results which may be of physiological and/or practical significance.

Key Words. Embryonic Stem Cells, Survival, Apoptosis, Cytokines/Chemokines, Hematopoietic Progenitors




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