Mesenchymal stem cell therapy for retro-corneal membrane – A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents. (December 2017)

• Record Type: Journal Article
• Authors: Rajendran, Vijayalakshmi; Netuková, Magdalena; Griffith, May; Forrester, John V; Kuffová, Lucia
• Is Part Of: Acta biomaterialia. Volume 64(2017)
• Page Start: 346
• Page End: 356
• Publication Date: 2017-12
• Subjects: Full-thickness collagen-based hydrogel implants -- Fibrin -- Retro-corneal membrane -- Mesenchymal stem cells; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2017.10.011
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: 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 membrane (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 clearance of gel-associated fibrin 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 Significance: The manuscript addresses the potential value 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 with mesenchymal stem cells reduces RCM formation and enhances corneal transparency.