July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Subconjunctival injection of low-dose mesenchymal stem cells promotes corneal allograft survival in a mouse cornea transplantation model
Author Affiliations & Notes
  • Thomas Ritter
    Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
  • Ellen Donohoe
    Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
  • Oliver Treacy
    Discipline of Pharmacology and Therapeutics, National University of Ireland Galway, Galway, Ireland
    Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
  • Kevin Lynch
    Discipline of Pharmacology and Therapeutics, National University of Ireland Galway, Galway, Ireland
    Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
  • Xizhe Chen
    Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
  • Gerry Fahy
    University Hospital Galway, Department of Ophthalmology, National University of Ireland Galway, Galway, Ireland
  • Aideen E Ryan
    Discipline of Pharmacology and Therapeutics, National University of Ireland Galway, Galway, Ireland
    Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
  • Nick Murphy
    Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
  • Footnotes
    Commercial Relationships   Thomas Ritter, None; Ellen Donohoe, None; Oliver Treacy, None; Kevin Lynch, None; Xizhe Chen, None; Gerry Fahy, None; Aideen Ryan, None; Nick Murphy, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4282. doi:
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      Thomas Ritter, Ellen Donohoe, Oliver Treacy, Kevin Lynch, Xizhe Chen, Gerry Fahy, Aideen E Ryan, Nick Murphy; Subconjunctival injection of low-dose mesenchymal stem cells promotes corneal allograft survival in a mouse cornea transplantation model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4282.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Systemic administration of mesenchymal stem/stromal cells (MSC) has been shown to promote corneal allograft survival in rodents. Here we investigate the potential of low-dose subconjunctival injection of MSC to promote corneal allograft survival in a mouse corneal transplant model.

Methods : MSC were isolated from 8 to 14-week-old female C57BL/6J (H-2k) or BALB/c (H-2d) mice or from healthy human donors and extensively characterised. A fully allogeneic mouse corneal transplant model was employed for these studies with BALB/c mice serving as recipients of female C57BL/6J grafts. A low-dose dual injection strategy was developed with mice receiving subconjunctival injections of 50.000 MSC on day -1 and day +1 before/after transplantation. Graft transparency was used as the primary indicator of rejection while neovascularisation was also recorded. To evaluate if MSC-injections modulate host immune cell populations, draining lymph node and spleen cells will be isolated from treated animals on day 2 and at the estimated time of rejection and characterised by flow cytometry.

Results : In vitro, MSC modulate key components of the corneal allograft rejection mechanisms by reprogramming macrophages to an anti-inflammatory phenotype and directly suppressing lymphocyte proliferation. In vivo, low-dose dual subconjunctival injection of 50.000 C57BL/6J MSC leads to 100% allograft survival in grafted mice (n=7). Interestingly, the same injection strategy using BALB/c (syngeneic) or human MSC (xenogeneic) only leads to 50% (n=8) or 30% graft survival (n=8), respectively, which is not significantly different from control transplanted mice (40%, n=6). With an aim to optimising administration strategies we also demonstrate that single administration of C57BL/6J MSC on either day -1 or day +1 promotes rejection free graft survival in 87% (n=8) and 85% (n=7) of grafted mice, respectively.

Conclusions : This work demonstrates that low-dose dual subconjunctival injection of allogeneic MSCs successfully promotes corneal allograft survival which can be optimised to a single administration strategy. Our data will contribute to defining the mechanism of action of MSC and refining future MSC-immunotherapies for prevention of corneal graft rejection in patients.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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