title: Mesenchymal stem cell therapy promotes corneal allograft survival in rats by local and systemic immunomodulation.
abstract: Mesenchymal stem cells (MSCs) are being investigated extensively due to their ability to dampen immune responses. Here, we tested the ability of MSCs from three distinct sources to prolong rat corneal allograft survival. A fully allogeneic rat cornea transplant model (DA to LEW) was used. Recipient rats received 1 × 10(6) MSCs (syn [LEW], allo [DA] or third-party [Wistar Furth]) intravenously 7 days before transplantation and again on the day of transplantation (day 0). A high percentage of untreated and syn-MSC treated allografts were rejected (80% and 100%, respectively). Preactivation of syn-MSCs with interferon gamma also failed to prolong allograft survival. Conversely, corneal allograft survival was significantly prolonged in allo-MSC treated (90%) and third-party MSC treated (80%) allograft recipients. Flow cytometric analysis revealed less infiltrating natural killer T cells in corneas of both allo- and third-party MSC treated animals, coupled with a higher proportion of splenic CD4+Foxp3+ regulatory T cells, compared to controls. In the case of allo- and third-party MSCs, results from a delayed-type hypersensitivity assay clearly showed that hypo-responsiveness was specific for corneal donor-associated allo-antigens. Thus, allo- and third-party MSC treatment prolongs corneal allograft survival by suppressing peripheral immune responses and promoting an intragraft immunoregulatory milieu.
authors.affiliation: College of Medicine, Nursing and Health Sciences, Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
authors.forename: O
authors.initials: O
authors.lastname: Treacy
authors.forename: L
authors.initials: L
authors.lastname: O'Flynn
authors.forename: A E
authors.initials: AE
authors.lastname: Ryan
authors.forename: M
authors.initials: M
authors.lastname: Morcos
authors.forename: P
authors.initials: P
authors.lastname: Lohan
authors.forename: S
authors.initials: S
authors.lastname: Schu
authors.forename: M
authors.initials: M
authors.lastname: Wilk
authors.forename: G
authors.initials: G
authors.lastname: Fahy
authors.forename: M D
authors.initials: MD
authors.lastname: Griffin
authors.forename: M
authors.initials: M
authors.lastname: Nosov
authors.forename: T
authors.initials: T
authors.lastname: Ritter
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001483:Base Sequence; D003316:Corneal Diseases / Q000601:surgery*; D017931:DNA Primers; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014184:Transplantation, Homologous
chemical_list: D000276:Adjuvants, Immunologic; D017931:DNA Primers
keywords: Basic (laboratory) research/science; corneal transplantation/ophthalmology; immune regulation; immunosuppression/immune modulation; regenerative medicine; stem cells; translational research/science