Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents

Vijayalakshmi Rajendran; Magdalena Netuková; May Griffith; John V Forrester; Lucia Kuffova

doi:10.1016/j.actbio.2017.10.011

Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents

Vijayalakshmi Rajendran, Magdalena Netuková, May Griffith, John V Forrester, Lucia Kuffova

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Pages (from-to)	346-356
Number of pages	11
Journal	Acta Biomaterialia
Volume	64
Early online date	10 Oct 2017
DOIs	https://doi.org/10.1016/j.actbio.2017.10.011
Publication status	Published - 31 Dec 2017

Bibliographical note

Acknowledgements: We would like to thank Mrs. R. Fordyce, University of Aberdeen, Scotland, UK for her diligent technical support; Mohammed Mirazul Islam, Linköpings Universitet, Sweden for preparing collagen-based hydrogels. They would also like to thank the Medical Research Facility (MRF), Ian Fraser Cytometry Centre (IFCC) and microscopy facility in University of Aberdeen for facilitating the in vivo and immunostaining experiments. The study is supported by the IGEN Centre, Linköping University and by grant from charity Saving Sight in Grampian, Development Trust, University of Aberdeen.

Keywords

Journal Article
full-thickness collagen-based hydrogel implants
fibrin
retro-corneal membrane
mesenchymal stem cells

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Cite this

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title = "Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents",

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.",

keywords = "Journal Article, full-thickness collagen-based hydrogel implants, fibrin, retro-corneal membrane, mesenchymal stem cells",

author = "Vijayalakshmi Rajendran and Magdalena Netukov{\'a} and May Griffith and Forrester, {John V} and Lucia Kuffova",

note = "Acknowledgements: We would like to thank Mrs. R. Fordyce, University of Aberdeen, Scotland, UK for her diligent technical support; Mohammed Mirazul Islam, Link{\"o}pings Universitet, Sweden for preparing collagen-based hydrogels. They would also like to thank the Medical Research Facility (MRF), Ian Fraser Cytometry Centre (IFCC) and microscopy facility in University of Aberdeen for facilitating the in vivo and immunostaining experiments. The study is supported by the IGEN Centre, Link{\"o}ping University and by grant from charity Saving Sight in Grampian, Development Trust, University of Aberdeen.",

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month = dec,

day = "31",

doi = "10.1016/j.actbio.2017.10.011",

language = "English",

volume = "64",

pages = "346--356",

journal = "Acta Biomaterialia",

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T1 - Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents

AU - Rajendran, Vijayalakshmi

AU - Netuková, Magdalena

AU - Griffith, May

AU - Forrester, John V

AU - Kuffova, Lucia

N1 - Acknowledgements: We would like to thank Mrs. R. Fordyce, University of Aberdeen, Scotland, UK for her diligent technical support; Mohammed Mirazul Islam, Linköpings Universitet, Sweden for preparing collagen-based hydrogels. They would also like to thank the Medical Research Facility (MRF), Ian Fraser Cytometry Centre (IFCC) and microscopy facility in University of Aberdeen for facilitating the in vivo and immunostaining experiments. The study is supported by the IGEN Centre, Linköping University and by grant from charity Saving Sight in Grampian, Development Trust, University of Aberdeen.

PY - 2017/12/31

Y1 - 2017/12/31

N2 - 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.

AB - 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.

KW - Journal Article

KW - full-thickness collagen-based hydrogel implants

KW - fibrin

KW - retro-corneal membrane

KW - mesenchymal stem cells

U2 - 10.1016/j.actbio.2017.10.011

DO - 10.1016/j.actbio.2017.10.011

M3 - Article

C2 - 29030302

SN - 1742-7061

VL - 64

SP - 346

EP - 356

JO - Acta Biomaterialia

JF - Acta Biomaterialia

ER -

Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents

Abstract

Bibliographical note

Keywords

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