Advanced Regenerative and REStorative Therapies to combat corneal BLINDNESS

Deliverables

Documents, reports (6)

All approvals package for multicenter Phase II study

All approvals from ethics committees and national competent authorities (if applicable) of all study sites once the last approval has been received.

Identification of the best location for cell harvesting

Identification of the best location for cell harvesting and optimal cell culture conditions, for human corneal endothelial cells.

Classification of LSCD by in vivo confocal microscopy

Classification of LSCD by in vivo confocal microscopy in the first 5 enrolled patients at UZA. Also includes limbal stem cell imaging prior to biopsy in donors. Training of UZA personnel for in vivo confocal microscopy examination of patients.

Final report on minipig study results

Manuscript describing results of minipig study, suitable for publication.

Report on feasibility of reducing antigenicity

Results of in vitro experiments with human cultured epithelial and endothelial cells from beneficiary LUMC. Cells obtained from UZA and NIIOS.

First study approvals package for Phase I Biocornea study

First study subject approvals package includes (prior to enrolment of first study subject): a. Final version of study protocol as submitted to regulators / ethics committee(s) b. Registration number of clinical study in a WHO- or ICMJE- approved registry c. Approvals (ethics committees and national competent authority if applicable) required for invitation / enrolment of first subject

Demonstrators, pilots, prototypes (1)

Identification of an optimum carrier for porcine cells

Identification of an optimum carrier material based on porcine endothelial cell expansion, adhesion, and biomechanical test data.

Websites, patent fillings, videos etc. (4)

Project website and promotional materials

Project website to communicate project results externally and to communicate/share documents internally within the consortium.

CE certified ologen™ Biocornea

Certificate of granted CE-mark to the Biocornea from the appropriate regulatory body.

Dissemination and Exploitation Strategy

Production and distribution of early project promotional materials, a communication strategy, and a dissemination strategy.

Marketing and business plan and final symposium

By the final year of the project, a market analysis and business plan will be delivered, and final conference symposium and communications report will be delivered.

Publications

Peer reviewed articles (30)

VEGF Trap R1R2 Suspended in the Semifluorinated Alkane F6H8 Inhibits Inflammatory Corneal Hem- and Lymphangiogenesis

Author(s): Viet Nhat Hung Le, Deniz Hos, Yanhong Hou, Madlen Witt, Mikhail Barkovskiy, Felix Bock, Claus Cursiefen
Published in: Translational Vision Science & Technology, 9/11, 2020, Page(s) 15, ISSN 2164-2591
Publisher: ARVO
DOI: 10.1167/tvst.9.11.15

Risk of Corneal Graft Rejection After High-risk Keratoplasty Following Fine-needle Vessel Coagulation of Corneal Neovascularization Combined With Bevacizumab: A Pilot Study

Author(s): Deniz Hos, Viet Nhat Hung Le, Martin Hellmich, Sebastian Siebelmann, Sigrid Roters, Bjoern O. Bachmann, Claus Cursiefen
Published in: Transplantation Direct, 5/5, 2019, Page(s) e452, ISSN 2373-8731
Publisher: The Transplantation Society
DOI: 10.1097/txd.0000000000000894

New developments in corneal endothelial cell replacement

Author(s): Daniele Spinozzi, Alina Miron, Marieke Bruinsma, Isabel Dapena, Viridiana Kocaba, Martine J. Jager, Gerrit R. J. Melles, Sorcha Ni Dhubhghaill, Silke Oellerich
Published in: Acta Ophthalmologica, 2021, ISSN 1755-375X
Publisher: Wiley-Blackwell
DOI: 10.1111/aos.14722

A porous collagen-based hydrogel and implantation method for corneal stromal regeneration and sustained local drug delivery

Author(s): Maria Xeroudaki, Muthukumar Thangavelu, Anton Lennikov, Anjula Ratnayake, Jovana Bisevac, Goran Petrovski, Per Fagerholm, Mehrdad Rafat, Neil Lagali
Published in: Scientific Reports, 10/1, 2020, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-020-73730-9

Göttingen Minipig is not a Suitable Animal Model for in Vivo Testing of Tissue-Engineered Corneal Endothelial Cell-Carrier Sheets and for Endothelial Keratoplasty

Author(s): Niklas Telinius, Daniele Spinozzi, Dusan Rasic, Isabel Dapena, Ulrik Baandrup, Alina Miron, Silke Oellerich, Jesper Hjortdal
Published in: Current Eye Research, 45/8, 2020, Page(s) 945-949, ISSN 0271-3683
Publisher: Swets & Zeitlinger
DOI: 10.1080/02713683.2019.1706747

Supplemental Anti Vegf A-Therapy Prevents Rebound Neovascularisation After Fine Needle Diathermy Treatment to Regress Pathological Corneal (LYMPH)Angiogenesis

Author(s): Viet Nhat Hung Le, Yanhong Hou, Felix Bock, Claus Cursiefen
Published in: Scientific Reports, 10/1, 2020, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-020-60705-z

A method for quantifying limbal stem cell niches using OCT imaging

Author(s): Michel Haagdorens, Joséphine Behaegel, Jos Rozema, Veerle Van Gerwen, Sofie Michiels, Sorcha Ní Dhubhghaill, Marie-José Tassignon, Nadia Zakaria
Published in: British Journal of Ophthalmology, 101/9, 2017, Page(s) 1250-1255, ISSN 0007-1161
Publisher: BMJ Publishing Group
DOI: 10.1136/bjophthalmol-2016-309549

Incidence and Clinical Course of Immune Reactions after Descemet Membrane Endothelial Keratoplasty

Author(s): Deniz Hos, Onur Tuac, Friederike Schaub, Tisha P. Stanzel, Silvia Schrittenlocher, Martin Hellmich, Björn O. Bachmann, Claus Cursiefen
Published in: Ophthalmology, 124/4, 2017, Page(s) 512-518, ISSN 0161-6420
Publisher: Elsevier BV
DOI: 10.1016/j.ophtha.2016.12.017

Improving the success rate of human corneal endothelial cell cultures from single donor corneas with stabilization medium

Author(s): D. Spinozzi, A. Miron, M. Bruinsma, J. T. Lie, I. Dapena, S. Oellerich, G. R. J. Melles
Published in: Cell and Tissue Banking, 19/1, 2018, Page(s) 9-17, ISSN 1389-9333
Publisher: Kluwer Academic Publishers
DOI: 10.1007/s10561-017-9665-y

UV light-blocking contact lenses protect against short-term UVB-induced limbal stem cell niche damage and inflammation

Author(s): M. Notara, S. Behboudifard, M. A. Kluth, C. Maßlo, C. Ganss, M. H. Frank, B. Schumacher, C. Cursiefen
Published in: Scientific Reports, 8/1, 2018, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-018-30021-8

Asymmetrical endothelial cell migration from in vitro Quarter-Descemet membrane endothelial keratoplasty grafts

Author(s): Alina Miron, Daniele Spinozzi, Marieke Bruinsma, Jessica T. Lie, Rénuka S. Birbal, Lamis Baydoun, Silke Oellerich, Gerrit R.J. Melles
Published in: Acta Ophthalmologica, 96/8, 2018, Page(s) 828-833, ISSN 1755-375X
Publisher: Wiley-Blackwell
DOI: 10.1111/aos.13841

Oxygen Tension Strongly Influences Metabolic Parameters and the Release of Interleukin-6 of Human Amniotic Mesenchymal Stromal Cells In Vitro

Author(s): Asmita Banerjee, Andrea Lindenmair, Ralf Steinborn, Sergiu Dan Dumitrescu, Simone Hennerbichler, Andrey V. Kozlov, Heinz Redl, Susanne Wolbank, Adelheid Weidinger
Published in: Stem Cells International, 2018, 2018, Page(s) 1-11, ISSN 1687-966X
Publisher: Hindawi
DOI: 10.1155/2018/9502451

UV light crosslinking regresses mature corneal blood and lymphatic vessels and promotes subsequent high-risk corneal transplant survival

Author(s): Yanhong Hou, Viet Nhat Hung Le, Gábor Tóth, Sebastian Siebelmann, Jens Horstmann, Tim Gabriel, Felix Bock, Claus Cursiefen
Published in: American Journal of Transplantation, 18/12, 2018, Page(s) 2873-2884, ISSN 1600-6135
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/ajt.14874

Fine Needle-Diathermy Regresses Pathological Corneal (Lymph)Angiogenesis and Promotes High-Risk Corneal Transplant Survival

Author(s): Viet Nhat Hung Le, Ann-Charlott Schneider, Rebecca Scholz, Felix Bock, Claus Cursiefen
Published in: Scientific Reports, 8/1, 2018, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-018-24037-3

Label-Free In Vivo Imaging of Corneal Lymphatic Vessels Using Microscopic Optical Coherence Tomography

Author(s): Jens Horstmann, Hinnerk Schulz-Hildebrandt, Felix Bock, Sebastian Siebelmann, Eva Lankenau, Gereon Hüttmann, Philipp Steven, Claus Cursiefen
Published in: Investigative Opthalmology & Visual Science, 58/13, 2017, Page(s) 5880, ISSN 1552-5783
Publisher: ARVO
DOI: 10.1167/iovs.17-22286

Novel Method to Detect Corneal Lymphatic Vessels In Vivo by Intrastromal Injection of Fluorescein

Author(s): Viet Nhat Hung Le, Yanhong Hou, Jens Horstmann, Felix Bock, Claus Cursiefen
Published in: Cornea, 37/2, 2018, Page(s) 267-271, ISSN 0277-3740
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/ico.0000000000001444

Photodynamic Therapy Leads to Time-Dependent Regression of Pathologic Corneal (Lymph) Angiogenesis and Promotes High-Risk Corneal Allograft Survival

Author(s): Yanhong Hou, Viet Nhat Hung Le, Thomas Clahsen, Ann-Charlott Schneider, Felix Bock, Claus Cursiefen
Published in: Investigative Opthalmology & Visual Science, 58/13, 2017, Page(s) 5862, ISSN 1552-5783
Publisher: ARVO
DOI: 10.1167/iovs.17-22904

Anterior segment optical coherence tomography for the diagnosis of corneal dystrophies according to the IC3D classification

Author(s): Sebastian Siebelmann, Paula Scholz, Simon Sonnenschein, Björn Bachmann, Mario Matthaei, Claus Cursiefen, Ludwig M. Heindl
Published in: Survey of Ophthalmology, 63/3, 2018, Page(s) 365-380, ISSN 0039-6257
Publisher: Elsevier BV
DOI: 10.1016/j.survophthal.2017.08.001

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy

Author(s): Federico Bech, Omar González-González, Enol Artime, Joana Serrano, Ignacio Alcalde, Juana Gallar, Jesús Merayo-Lloves, Carlos Belmonte
Published in: Investigative Opthalmology & Visual Science, 59/6, 2018, Page(s) 2281, ISSN 1552-5783
Publisher: ARVO
DOI: 10.1167/iovs.18-24007

Evaluation of the Suitability of Biocompatible Carriers as Artificial Transplants Using Cultured Porcine Corneal Endothelial Cells

Author(s): Daniele Spinozzi, Alina Miron, Marieke Bruinsma, Isabel Dapena, Itay Lavy, Perry S. Binder, Mehrdad Rafat, Silke Oellerich, Gerrit R.J. Melles
Published in: Current Eye Research, 2018, Page(s) 1-7, ISSN 0271-3683
Publisher: Swets & Zeitlinger
DOI: 10.1080/02713683.2018.1536215

Ethical issues in living-related corneal tissue transplantation

Author(s): Joséphine Behaegel, Sorcha Ní Dhubhghaill, Heather Draper
Published in: Journal of Medical Ethics, 45/7, 2019, Page(s) 430-434, ISSN 0306-6800
Publisher: BMJ Publishing Group
DOI: 10.1136/MEDETHICS-2018-105146

Short- and Long-Term Results of Xenogeneic-Free Cultivated Autologous and Allogeneic Limbal Epithelial Stem Cell Transplantations

Author(s): Joséphine Behaegel, Nadia Zakaria, Marie-José Tassignon, Inge Leysen, Felix Bock, Carina Koppen, Sorcha Ní Dhubhghaill
Published in: Cornea, 38/12, 2019, Page(s) 1543-1549, ISSN 0277-3740
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/ico.0000000000002153

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Author(s): Neil Lagali
Published in: Current Eye Research, 2019, Page(s) 1-13, ISSN 0271-3683
Publisher: Swets & Zeitlinger
DOI: 10.1080/02713683.2019.1663874

Corneal epithelial restoration after penetrating keratoplasty in repeated failed cultivated limbal stem cell grafts

Author(s): Joséphine Behaegel, Carina Koppen, Veerle Van Gerwen, Marie-José Tassignon, Sorcha Ní Dhubhghaill
Published in: Journal of EuCornea, 2, 2019, Page(s) 6-9, ISSN 2452-4034
Publisher: Elsevier
DOI: 10.1016/j.xjec.2019.03.001

In vitro endothelial cell migration from limbal edge-modified Quarter-DMEK grafts

Author(s): Alina Miron, Daniele Spinozzi, Sorcha Ní Dhubhghaill, Jessica T. Lie, Silke Oellerich, Gerrit R. J. Melles
Published in: PLOS ONE, 14/11, 2019, Page(s) e0225462, ISSN 1932-6203
Publisher: Public Library of Science
DOI: 10.1371/journal.pone.0225462

Development and Validation of an Open-Source Grading Tool for Outcome Assessment in Limbal Stem Cell Treatment

Author(s): Joséphine Behaegel, Alejandra Consejo, Kristien Wouters, Carina Koppen, Joost De Cock, Sorcha Ní Dhubhghaill
Published in: Cornea, 39/6, 2020, Page(s) 787-792, ISSN 0277-3740
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/ico.0000000000002282

Safety of Cultivated Limbal Epithelial Stem Cell Transplantation for Human Corneal Regeneration

Author(s): J. Behaegel, S. Ní Dhubhghaill, C. Koppen, N. Zakaria
Published in: Stem Cells International, 2017, 2017, Page(s) 1-11, ISSN 1687-966X
Publisher: Hindawi Limited
DOI: 10.1155/2017/6978253

In Vitro Evaluation and Transplantation of Human Corneal Endothelial Cells Cultured on Biocompatible Carriers

Author(s): Daniele Spinozzi, Alina Miron, Jessica T. Lie, Mehrdad Rafat, Neil Lagali, Gerrit R.J. Melles, Sorcha Ni Dhubhghaill, Isabel Dapena, Silke Oellerich
Published in: Cell Transplantation, 29, 2020, Page(s) 096368972092357, ISSN 0963-6897
Publisher: Cognizant Communication Corp.
DOI: 10.1177/0963689720923577

Corneal Crosslinking to Regress Pathologic Corneal Neovascularization Before High-Risk Keratoplasty

Author(s): Friederike Schaub, Yanhong Hou, Wei Zhang, Felix Bock, Deniz Hos, Claus Cursiefen
Published in: Cornea, 40/2, 2021, Page(s) 147-155, ISSN 0277-3740
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/ico.0000000000002406

Outcomes of Human Leukocyte Antigen–Matched Allogeneic Cultivated Limbal Epithelial Transplantation in Aniridia-Associated Keratopathy—A Single-Center Retrospective Analysis

Author(s): Joséphine Behaegel, Marie-José Tassignon, Neil Lagali, Alejandra Consejo, Carina Koppen, Sorcha Ní Dhubhghaill
Published in: Cornea, Publish Ahead of Print, 2021, ISSN 0277-3740
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1097/ico.0000000000002729

Thesis dissertations (1)

The Bigger Picture of Ex Vivo Limbal Epithelial Stem Cell Transplantation

Author(s): Joséphine Behaegel
Published in: PhD Dissertation, 2019
Publisher: Academic and Scientific Publishers

Book chapters (2)

Cultivated Limbal Stem Cell Transplantation: Indications and Technique

Author(s): Joséphine Behaegel, Sorcha Ní Dhubhghaill, Marie-José Tassignon
Published in: Corneal Regeneration - Therapy and Surgery, Jan 2019, 2019, Page(s) 277-290, ISBN 978-3-030-01303-5
Publisher: Springer International Publishing
DOI: 10.1007/978-3-030-01304-2_19

CORNEAL NEOVASCULARIZATION: UPDATE ON PATHOGENESIS AND ADVANCES IN TREATMENT STRATEGIES

Author(s): Joséphine Behaegel, Sorcha Ní Dhubhghaill, Carina Koppen, Nadia Zakaria
Published in: International Journal of Medical and Biological Frontiers;, Vol 22, 2016, ISSN 1081-3829
Publisher: Nova Science Publishers

Conference proceedings (1)

Need for technologies in advanced corneal research, diagnosis, and transplantation

Author(s): Neil S. Lagali
Published in: Ophthalmic Technologies XXIX, 2019, Page(s) 82, ISBN 9781-510623590
Publisher: SPIE
DOI: 10.1117/12.2520656