HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nitsche, A. Articles by Siegert, W. Search for Related Content PubMed PubMed Citation Articles by Nitsche, A. Articles by Siegert, W.

Interleukin-3 Promotes Proliferation and Differentiation of Human Hematopoietic Stem Cells but Reduces Their Repopulation Potential in NOD/SCID Mice

Andreas Nitsche^a,b, Ilse Junghahn^c, Stefanie Thulke^a, Jutta Aumann^c, Aleksandar Radoni^a, Iduna Fichtner^c, Wolfgang Siegert^a

^a Medizinische Klinik II, Charité-Campus Charité Mitte, Humboldt Universität zu Berlin, Germany;
^b Robert Koch-Institute, Berlin, Germany;
^c Department of Experimental Pharmacology, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany

Key Words. NOD/SCID mice • Hematopoietic • Stem cell • Engraftment • Interleukin 3 • Immunochecmistry

Wolfgang Siegert, M.D., Medizinische Klinik II, Charite-Campus Charite Mitte, Schumannstr. 20/21, 10117 Berlin, Germany. Telephone: 49-30-450-513144 or 49-30-450-513002 (Secretariat); Fax: 49-30-450-513952; e-mail: wolfgang.siegert{at}charite.de

In the present study we explored systematically the influence of human interleukin-3 (IL-3) on the cord blood (CB) cell-derived production of human hematopoietic cells in the bone marrow, blood, and spleen of chimeric nonobese/severe combined immunodeficient mice ((NOD/SCID) mice. CB mononuclear cells and MACS-enriched CB CD34⁺ cells were injected into irradiated NOD/SCID mice. The mice were additionally transplanted with a stably transfected rat fibroblast cell line expressing the human IL-3 gene (Rat-IL-3) constitutively, or with the nontransfected rat fibroblast cell line as a control (Rat-1). Rat-IL-3 mice displayed a higher engraftment of human hematopoietic cells in bone marrow, spleen, and peripheral blood compared with mice with Rat-1 cotransplantation. When we transplanted their total bone marrow cell population into secondary mice, surprisingly, mice transplanted with bone marrow cells from Rat-1 mice displayed a higher proportion of human hematopoietic cells compared with Rat-IL-3 mice. As expected, bone marrow cultures (BMCs) from Rat-IL-3 mice contained a higher proportion of human cells than Rat-1 bone marrow cells. However, when BMCs were passaged to new flasks, we observed a higher proportion of human cells in BMCs from Rat-1 mice compared with BMCs from Rat-IL-3 mice. IL-3 promotes the proliferation and differentiation of hematopoietic stem cells in chimeric bone marrow. In addition, IL-3 may play a role in the depletion of hematopoietic stem cells in chimeric bone marrow. In the absence of IL-3, the hematopoietic stem cells may remain in a quiescent state and proliferation can be induced by stimuli, including secondary transplantation or cell passage.