Document Detail


Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate.
MedLine Citation:
PMID:  18762258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The induction of tolerance towards allogeneic solid organ grafts is one of the major goals in transplantation medicine. Mesenchymal stem cells (MSC) inhibit the immune response in vitro, and thus are promising candidate cells to promote acceptance of transplanted organs in vivo. Such novel approaches of tolerance induction are needed since, to date, graft acceptance can only be maintained through life-long treatment with unspecific immunosuppressants that are associated with toxic injury, opportunistic infections and malignancies. We demonstrate that donor-derived MSC induce long-term allograft acceptance in a rat heart transplantation model, when concurrently applied with a short course of low-dose mycophenolate. This tolerogenic effect of MSC is at least partially mediated by the expression of indoleamine 2,3-dioxygenase (IDO), demonstrated by the fact that blocking of IDO with 1-methyl tryptophan (1-MT) abrogates graft acceptance. Moreover we hypothesize that MSC interact with dendritic cells (DC) in vivo, because allogeneic MSC are rejected in the long-term but DC acquire a tolerogenic phenotype after applying MSC. In summary, we demonstrate that MSC constitute a promising tool for induction of non-responsiveness in solid organ transplantation that warrants further investigation in clinical trials.
Authors:
F C Popp; E Eggenhofer; P Renner; P Slowik; S A Lang; H Kaspar; E K Geissler; P Piso; H J Schlitt; M H Dahlke
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-30
Journal Detail:
Title:  Transplant immunology     Volume:  20     ISSN:  0966-3274     ISO Abbreviation:  Transpl. Immunol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-18     Completed Date:  2009-03-09     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9309923     Medline TA:  Transpl Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  55-60     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Regensburg, Franz-Josef-Strauss Allee, 11 93053 Regensburg, Germany. felix.popp@klinik.uni-regensburg.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Dendritic Cells / immunology
Graft Rejection / prevention & control*
Graft Survival / drug effects,  immunology*
Heart Transplantation* / pathology
Immunosuppression / methods*
Immunosuppressive Agents / administration & dosage*
Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors,  metabolism
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stromal Cells / drug effects,  immunology*
Mycophenolic Acid / administration & dosage,  analogs & derivatives*
Rats
T-Lymphocytes, Regulatory / immunology,  metabolism
Tryptophan / analogs & derivatives,  pharmacology
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 24280-93-1/Mycophenolic Acid; 73-22-3/Tryptophan; 7303-49-3/tryptophan methyl ester; 9242ECW6R0/mycophenolate mofetil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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