Mesenchymal Stem Cell Therapy for Retro-Corneal Membrane – a Clinical Challenge in Full-thickness Transplantation of Biosynthetic Corneal Equivalents

Publication date: Available online 10 October 2017
Source:Acta Biomaterialia
Author(s): Vijayalakshmi Rajendran, Magdalena Netuková, May Griffith, John V Forrester, Lucia Kuffová
Artificial corneas (keratoprostheses) and biosynthetic collagen-based corneal equivalents are surgical implants designed to ease the global burden of corneal blindness. However, keratoprostheses in many cases fail due to development of fibrous retro-corneal membranes (RCM). Fibrous membranes which develop in the anterior chamber after prosthesis implantation do so on a matrix of fibrin. This study investigated fibrin deposition and RCM formation after full-thickness collagen-based hydrogel implants and compared them with syngeneic and allogeneic corneal grafts in mice. Fibrin cleared from the anterior chamber within 14 days in both allo- and syn-grafts but, persisted in hydrogel implants and developed into dense retro-corneal sheets (RCM) which were heavily infiltrated by activated myofibroblasts. In contrast, the number of CD11b⁺ macrophages) infiltrating the initial deposition of fibrin in the anterior chamber (AC) after hydrogel implantation was markedly reduced compared to syn- and allo-grafts. Inoculation of mesenchymal stem cells prior to collagen gel implant promoted of gel-associated fibrin clearance from the anterior chamber. We propose that a failure of macrophage-mediated clearance of fibrin may be the cause of RCM formation after collagen-based hydrogel implants and that mesenchymal stem cell therapy promotes clearance of fibrin and prevents RCM formation.Statement of significanceThe manuscript addresses the significance of bone marrow-derived mesenchymal stem cell therapy for retro-corneal membrane (RCM) formation in full-thickness transplantation of biosynthetic corneal equivalents. This work reports the pathophysiological changes in the anterior chamber of the mouse eye following full-thickness recombinant human cross-linked collagen-based hydrogel implants in which persistent fibrin promotes the development of dense RCM. Furthermore, pre-treatment of anterior segment of the mouse eye with mesenchymal stem cells reduces RCM formation and enhances corneal transparency.

Graphical abstract

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