Comparative effects of in vivo treatment using interleukin-11 and stem cell factor on reconstitution in mice after bone marrow transplantation.
Molecular analysis of the hematopoietic microenvironment (HM) has led to the characterization and molecular cloning of two unique growth factors produced by stromal cells. Interleukin (IL)-11 and stem-cell factor (SCF; steel factor [SF]) have been shown in a variety of in vitro culture systems to stimulate distinct populations of stem, progenitor, and more differentiated cell types. We have analyzed and compared the effects of each growth factor administered to mice undergoing bone marrow transplantation (BMT) after total body irradiation (TBI). We report that IL-11 stimulates platelet and neutrophil recovery, while the main effect of SCF is on erythroid cell recovery in this model. Mice treated with the combination of IL-11 and SCF show increases in all three lineages compared with control mice, without obvious toxicity. In addition, both the type of progenitor- and stem-cell populations stimulated and the anatomic localization of effects seen with each growth factor are distinct. These data in mice suggest that the combination of IL-11 and SCF might be useful in humans undergoing myeloablative therapies.
Du
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Herman B Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, Indianapolis, IN.
Keller
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Maze
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Williams
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DA
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D017370:Interleukin-11 / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology; D019089:Stem Cell Factor; D013997:Time Factors
D016298:Hematopoietic Cell Growth Factors; D017370:Interleukin-11; D011994:Recombinant Proteins; D019089:Stem Cell Factor