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Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents
University of Aberdeen, Scotland.
Charles University of Prague, Czech Republic.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. University of Montreal, Canada.ORCID iD: 0000-0003-1222-6720
University of Aberdeen, Scotland; University of Western Australia, Australia; Lions Eye Institute, Australia.
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2017 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 64, p. 346-356Article in journal (Refereed) Published
Abstract [en]

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 CD11 b(+) 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. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2017. Vol. 64, p. 346-356
Keywords [en]
Full-thickness collagen-based hydrogel implants; Fibrin; Retro-corneal membrane; Mesenchymal stem cells
National Category
Biomaterials Science
Identifiers
URN: urn:nbn:se:liu:diva-143728DOI: 10.1016/j.actbio.2017.10.011ISI: 000416498200031PubMedID: 29030302OAI: oai:DiVA.org:liu-143728DiVA, id: diva2:1166737
Note

Funding Agencies|IGEN Centre, Linkoping University; charity Saving Sight in Grampian, Development Trust, University of Aberdeen

Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2017-12-15

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