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Third-party allogeneic mesenchymal stromal cells prevent rejection in a pre-sensitized high-risk model of corneal transplantation
Lohan, Paul; Murphy, Nick; Treacy, Oliver; Lynch, Kevin; Morcos, Maurice; Bingling, Chen; Ryan, Aideen E.; Griffin, Matthew D.; Ritter, Thomas
High-risk cornea transplant recipients represent a patient population with significant un-met medical need for more effective therapies to prevent immunological graft rejection due to heightened anti-donor immune response. In this study, a rat model of pre-existing anti-donor immunity was developed in which comeal allografts were rejected earlier than in non-pre-sensitized recipients. In this model, third-party (non-donor, non-recipient strain) allogeneic mesenchymal stromal cells (allo-MSC) were administered intravenously 7 and 1 days prior to transplantation. Rejection-free graft survival to 30 days post-transplant improved from 0 to 63.6% in MSC-treated compared to vehicle-treated control animals (p = This study was supported by the EU FP7 Collaborative Health Project VISICORT (grant number 602470; PL, MG, and TR) and by a Science Foundation Ireland Investigator Award (grant number 12/IA/1624; NM, OT, KL, MM, BC, and TR). The authors have also received support from a Science Foundation Ireland Strategic Research Cluster Award (REMEDI, grant number 09/SRC-B1794; AER, MG, and TR), a Science Foundation Ireland Research Centers Award (CÚRAM, grant number 13/RC/2073, MG), the EU Horizon 2020 Collaborative Health Project NEPHSTROM (grant number 634086; MG), an Irish Cancer Society Fellowship (grant number CRF12RYA; AR), a Science Foundation Ireland Starting Investigator Grant (grant number 15/SIRG/3456; AR), support from Galway Foundation and the European Regional Development Fund. The authors wish to acknowledge the advice, assistance and technical expertise of Ms. Aoife Duffy of the Center for Cell Manufacturing Ireland, NUI Galway and the Flow Cytometry Core Facility, NUI Galway. All flow cytometry experiments were performed in the NUI Galway Flow Cytometry Core Facility which is supported by funds from NUI Galway, Science Foundation Ireland, the Irish Government's Programme for Research in Third Level Institutions, Cycle 5 and the European Regional Development Fund.
Keyword(s): Mesenchymal stromal cells; Cornea transplantation; High-risk; Pre-sensitization; Regulatory T cells; Immunomodulation; Third-party; REGULATORY T-CELLS; STEM-CELLS; ALLOGRAFT SURVIVAL; MEDIATED IMMUNOSUPPRESSION; GRAFT-REJECTION; THERAPY; TOLERANCE; DRUGS; LUNG; RATS
Publication Date:
2018
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Contributor(s): Seventh Framework Programme; Science Foundation Ireland; Horizon 2020; Irish Cancer Society; Galway University Foundation; European Regional Development Fund
Institution: NUI Galway
Publisher(s): Frontiers Media
File Format(s): application/pdf
First Indexed: 2019-03-23 06:45:13 Last Updated: 2019-09-20 06:42:43