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Title: Role of mesenchymal stem cells and collagen-based corneal equivalents in restoring corneal graft transparency
Author: Rajendran, Vijayalakshmi
ISNI:       0000 0004 6353 2207
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2016
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Corneal blindness is one of the leading causes of vision loss worldwide mainly due to infection/injury. Generally, the damaged corneas are surgically replaced by corneal transplantation to restore vision. Corneal allografts display very high success rates amongst other solid organ transplants, despite no tissue matching and no systemic immunosuppression. Although high success rates of corneal transplants are observed in non-inflamed "low-risk" graft beds, poor prognosis is observed in "high-risk" corneal graft beds due to pre-existing inflammation and vascularization. The significant decrease in the corneal allograft acceptance rate in "high-risk" settings remains an immunological challenge for a long-term survival. To address this clinical problem along with the prevailing shortage of donor corneas, two new lines of therapeutic approaches for corneal graft rejection have been developed: (1) bone marrow derived mesenchymal stem cells (BM-MSC) based therapy and (2) bioengineered collagenbased corneal equivalents. Both are investigated in this thesis using a fully MHC mismatched murine model of corneal allograft transplantation. In the first approach, I found that the strain and route of BM-MSC administration play a vital role in restoring corneal graft clarity. Only intravenous (i.v.) treatment of allogeneic-BM-MSC was shown to significantly reduce corneal allograft opacity, but not syngeneic-BM-MSC. In addition, among the investigated routes of BM-MSC administration – (1) i.v., (2) subconjunctival and (3) anterior chamber (AC), only AC route of treatment has shown significantly prolonged corneal allograft survival and graft clarity. In the second approach, I found that the main problem was not immune rejection as both collagen mimetic peptides and recombinant human collagen hydrogels invariably elicit minimal dendritic cell responses, but the formation of a dense fibrous membrane around the hydrogel implants. Furthermore, persistence of fibrin and a-SMA+ myofibroblasts was observed in AC of full-thickness hydrogel grafts. In addition, lack of sufficiently infiltrated macrophages in AC of hydrogel grafts correlated with a lack of fibrin clearance which leads to the fibrous retro-corneal membrane formation. Injection of BM-MSC into the AC of hydrogel grafts has shown to be effectively involved in fibrin clearance and in restoring hydrogel graft clarity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Mesenchymal stem cells ; Cornea ; Transparency