title: Mesenchymal stem cells home to inflamed ocular surface and suppress allosensitization in corneal transplantation.
abstract: OBJECTIVE
  To investigate whether systemically injected syngeneic mesenchymal stem cells (MSCs) can home to the transplanted cornea, suppress induction of alloimmunity, and promote allograft survival.
  
  
  METHODS
  Mesenchymal stem cells were generated from bone marrow of wild-type BALB/c or GFP (green fluorescent protein)+ C57BL/6 mice, and 1×10(6) cells were intravenously injected to allografted recipients 3 hours after surgery. Mesenchymal stem cells homing to the cornea were examined at day 3 post transplantation by immunohistochemistry. MHC (major histocompatibility complex) II+CD11c+ cells were detected in the cornea and lymph nodes (LNs) 14 days post transplantation using flow cytometry. Cytokine expression of bone marrow-derived dendritic cells (BMDCs) was determined using real-time PCR. ELISPOT assay was used to assess indirect and direct host T cell allosensitization, and graft survival was evaluated by slit-lamp biomicroscopy weekly up to 8 weeks.
  
  
  RESULTS
  Intravenously injected GFP+ MSCs were found in abundance in the transplanted cornea, conjunctiva, and LNs, but not in the ungrafted (contralateral) tissue. The frequencies of mature MHC II+CD11c+ antigen-presenting cells (APCs) were substantially decreased in the corneas and draining LNs of MSC-injected allograft recipients compared to control recipients. Maturation and function of in vitro cultured BMDCs were decreased when cocultured with MSCs. Draining LNs of MSC-injected allograft recipients showed lower frequencies of IFNγ-secreting Th1 cells compared to the control group. Allograft survival rate was significantly higher in MSC-injected recipients compared to non-MSC-injected recipients.
  
  
  CONCLUSIONS
  Our data demonstrate that systemically administered MSCs specifically home to the inflamed ocular surface and promote allograft survival by inhibiting APC maturation and induction of alloreactive T cells.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Omoto
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Kishore R
authors.initials: KR
authors.lastname: Katikireddy
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rezazadeh
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Dohlman
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002478:Cells, Cultured; D016039:Corneal Transplantation / Q000379:methods*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005126:Eye Burns / Q000139:chemically induced / Q000473:pathology / Q000601:surgery; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D012313:RNA
keywords: allosensitization; antigen-presenting cells; cornea transplantation; homing; mesenchymal stem cells