Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model.
Recent studies indicate that mesenchymal stem cells (MSC) exhibit a degree of immune privilege due to their ability to suppress T cell mediated responses causing tissue rejection; however, the impact of allogeneic MSC in the setting of organ transplantation has been poorly investigated so far. The aim of our study was to evaluate the effect of intravenous donor MSC infusion for clinical tolerance induction in allogeneic skin graft transplantations in rats. MSC were isolated from Wistar rats and administered in Sprague-Dawley rats receiving Wistar skin graft with or without cyclosporine A (CsA). Graft biopsies were performed at day 10 post transplantation in all experimental groups for histological and gene expression studies. Intravenous infusion with donor MSC in CsA-treated transplanted rats resulted in prolongation of skin allograft survival compared to control animals. Unexpectedly, donor MSC infusion in immunocompetent rats resulted in a faster rejection as compared to control group. Cytokine expression analysis at the site of skin graft showed that CsA treatment significantly decreased pro-inflammatory cytokines IFN-gamma and IL-2 and reduced TNF-alpha gene expression; however, the level of TNF-alpha is high in MSC-treated and not immunosuppressed rats. Results of our study in a rat tissue transplantation model demonstrated a possible immunogenic role for donor (allogeneic) MSC, confirming the need of adequate preclinical experimentation before clinical use.
Sbano
Paolo
P
Department of Clinical Medicine and Immunological Sciences, Section of Dermatology, University of Siena, Siena, Italy.
Cuccia
Aldo
A
Mazzanti
Benedetta
B
Urbani
Serena
S
Giusti
Betti
B
Lapini
Ilaria
I
Rossi
Luciana
L
Abbate
Rosanna
R
Marseglia
Giuseppina
G
Nannetti
Genni
G
Torricelli
Francesca
F
Miracco
Clelia
C
Bosi
Alberto
A
Fimiani
Michele
M
Saccardi
Riccardo
R
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D006082:Graft Enhancement, Immunologic; D006084:Graft Rejection / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016038:Skin Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine