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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2189-2197. Prepublished online as a Blood First Edition Paper on November 2, 2004; DOI 10.1182/blood-2004-07-2757. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2757v1 105/5/2189    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chilton, P. M. Articles by Ildstad, S. T. Search for Related Content PubMed PubMed Citation Articles by Chilton, P. M. Articles by Ildstad, S. T. Related Collections Transplantation Free Research Articles Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients Paula M. Chilton, Francine Rezzoug, Mariusz Z. Ratajczak, Isabelle Fugier-Vivier, Janina Ratajczak, Magda Kucia, Yiming Huang, Michael K. Tanner, and Suzanne T. Ildstad From the Institute for Cellular Therapeutics, University of Louisville, KY. Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage–colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell–derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. F. N. Chan, H. Razavy, B. Luo, A. M. J. Shapiro, and C. C. Anderson Development of Either Split Tolerance or Robust Tolerance along with Humoral Tolerance to Donor and Third-Party Alloantigens in Nonmyeloablative Mixed Chimeras J. Immunol., April 15, 2008; 180(8): 5177 - 5186. [Abstract] [Full Text] [PDF]

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