Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats

Abstract We investigated the effect of autologous mesenchymal stem cells (MSC) on multiple unmodified donor bone marrow (BM) infusions and vascularized skin graft outcome. BM-derived rat MSC were examined for phenotype and function. MSC/MSC-conditioned-medium suppressed IFN-γ production by T cells a...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2008-06, Vol.127 (3), p.348-358
Main Authors: Aksu, Ali Emre, Horibe, Elaine, Sacks, Justin, Ikeguchi, Ryosuke, Breitinger, Jeremy, Scozio, Merissa, Unadkat, Jignesh, Feili-Hariri, Maryam
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Biological and medical sciences
Bone marrow
Bone Marrow - immunology
Bone Marrow - metabolism
Bone Marrow Transplantation - immunology
Culture Media, Conditioned
Cytokines - immunology
Cytokines - metabolism
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Graft Survival - immunology
Graft vs Host Disease - immunology
Graft vs Host Disease - therapy
GVHD
Interferon-gamma - biosynthesis
Interferon-gamma - immunology
Mesenchymal Stem Cell Transplantation
Mesenchymal stem cells
Mesenchymal Stromal Cells - immunology
Mesenchymal Stromal Cells - metabolism
Rat
Rats
Rats, Inbred Lew
Rats, Wistar
Skin Transplantation
Transplantation Chimera
Vascularized skin
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Summary:Abstract We investigated the effect of autologous mesenchymal stem cells (MSC) on multiple unmodified donor bone marrow (BM) infusions and vascularized skin graft outcome. BM-derived rat MSC were examined for phenotype and function. MSC/MSC-conditioned-medium suppressed IFN-γ production by T cells and modified DC function. Infusions of MSC with one-time BM improved vascularized skin graft survival, while with one–two-times BM reversed graft versus host disease (GVHD). Mixed chimerism was enhanced in recipients given two–four-times BM with MSC infusions. Interestingly, four-times BM infusions with MSC delayed GVHD onset, reduced host tissue damage and enhanced vascularized skin allograft survival compared to four-times BM alone. These data demonstrate that, the co-infusion of MSC with unmodified BM limit the toxicity of allogeneic BM transplantation, enhance mixed chimerism and improve vascularized skin graft survival. These findings provide insights for the development of autologous MSC-based BM transplantation and prevention of graft rejection or treatment of autoimmunity.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2008.02.003