Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats.
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-gamma 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.
Aksu
Ali Emre
AE
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Horibe
Elaine
E
Sacks
Justin
J
Ikeguchi
Ryosuke
R
Breitinger
Jeremy
J
Scozio
Merissa
M
Unadkat
Jignesh
J
Feili-Hariri
Maryam
M
D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology*; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D016038:Skin Transplantation; D018183:Transplantation Chimera
D017077:Culture Media, Conditioned; D016207:Cytokines; D007371:Interferon-gamma