To evaluate the effectiveness of cultured human limbal epithelium for the treatment of limbal stem cell deficiency

Lead Research Organisation: Newcastle University
Department Name: Institute of Human Genetics

Abstract

The cornea is the clear window at the front of the eye and its clarity is vital for light transmission to the back of the eye for visual perception. Transparency of the cornea depends upon the integrity of its outermost layer called the epithelium, which is constantly regenerated throughout life by a population of stem cells found at the edge of the cornea in an area called the limbus, the so called limbal stem cells (LSC). If LSC becomes deficient as a result of injury or disease, this epithelium will breakdown leading to severe pain and blindness. This condition is often difficult to treat, however, the management of limbal stem cell deficiency (LSCD) has benefited from major breakthroughs in recent years. LSC from the patient?s own (one eye disease) or a relative healthy eye or from a cadaveric eye can grow in the laboratory and then transplanted to the diseased eye. This technique however uses animal products to help grow the cells with a great risk of diseases transmission. In addition, the safety and effectiveness of this treatment is rather difficult to establish due to the diversity and the small number of cases reported. Transplantation of cultured limbal epithelium can therefore not be recognized, enabling NHS funding, until its effectiveness and safety is determined by a formally structured clinical trial. Such a trial forms the main objective of this proposal. We have therefore developed an ?animal product free? technique for growing the cells in the laboratory in an ultra-clean environment and successfully transplanted 8 patients with LSCD in one eye by taking LSC from their healthy other eye. Despite of our success, this number of patients is not significant to draw proper conclusions. This proposal aims therefore to evaluate the safety and efficacy of our methods by treating more patients with total unilateral LSCD. Another aim of the project is to develop a freezing method of cultured human LSC for storage and to set-up a service to supply clinical grade cultured LSC for transplantation at other UK centres. In addition, this study will investigate the abnormal tear film in patients with LSCD to allow for a customised eye treatment. Finally, LSCD has an enormous impact on patient?s quality of life with serious detrimental effects on productivity and leisure activities. To that effect we have selected 4 questionnaires to look at different aspects of patients with LSCD and its treatment.

Technical Summary

Limbal stem cell deficiency (LSCD) is a disease caused by the loss or dysfunction of limbal stem cells (LSC). In LSCD, the corneal epithelium integrity and function cannot be maintained and consequently epithelial defects occur causing persistent pain and severe visual impairment with marked patient morbidity, often affecting young adults and requiring frequent clinic visits. By far the most common cause is from chemical burns. The management of severe LSCD has benefited from major breakthroughs in recent years. In 1989, it was proposed that tissue limbal grafts could be used to treat LSCD. This involved tissue from the patient?s other healthy eye (autografts in unilateral cases) or from a living relative or cadaver (allografts in bilateral cases). In cases of autografts and living relatives, the donor eye is at risk of developing iatrogenic LSCD due to the large amounts of tissue required. In cases of allografts, systemic immunosuppression is required which is associated with enormous risk of toxicity. In 1997, Pellegrini and co-workers described a procedure using a small piece of autologous limbal tissue cultivated in vitro to treat two patients with unilateral alkali burns. This significantly reduces the risk of causing LSCD in the donor eye and eliminates the requirement of immunosuppression. Subsequently, other studies have been conducted, however the effectiveness of this treatment is impossible to establish due to the small number of cases reported and the heterogeneity of the studies. Transplantation of cultured limbal epithelium can therefore not be recognized as a treatment option for LSCD, enabling NHS funding, until its safety and effectiveness is established by a formally structured clinical trial. Such a trial forms the main objective of this proposal. We have successfully treated 8 consecutive patients with total unilateral LSCD using ex vivo expanded (animal free system and full GMP conditions) LSC autografts. Aims of this study is to evaluate:
? The safety and effectiveness of cultured human LSC for the treatment of patients with unilateral total LSCD;
? Patients reported outcomes before and after LSC transplantation;
? The tear film of patients with unilateral LSCD before and after LSC transplantation;
? The predictive value of pre-operative OCT in terms of visual outcomes and the need for further surgery, e.g., penetrating keratoplasty;
? To develop a cryopreservation method of culturing human LSC for storage and to set-up a national service to supply clinical grade ex vivo expanded LSC for transplantation at other UK centres.

Publications

10 25 50
 
Description Home Office Special Meeting on Corrosive Attack
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact The UK currently has one of the highest rate of corrosive attacks per person of any country in the world. More than 400 attacks were recorded up to April 2017. This meeting at the Home Office in London aimed to discuss increased levels of corrosive attacks in the UK over the last 2 years. The Home Office is currently drawing up draft legislation targeting acid attacks, which could bring in punishments for anyone carrying corrosive substances without justification and restrict purchases. The police are currently carrying out a survey across England and Wales, with the results due in February 2018, and the Home Office has commissioned separate research seeing convicted attackers interviewed to learn more about their motivations. There has been agreements already in place with some retailers to stop the sale of the most harmful liquids or impose age restrictions and identification checks. The emergency services have developed a joint protocol to ensure they can provide the same first aid to victims and preserve evidence at the scene, while every police officer in the country is being given specific training over the coming 12 months.
 
Description International Limbal Stem Cell Workshop
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Invited Member of the European Eye Bank Assocaition Special Interest Group for "Advanced Therapy Medicinal Products" since Feb 2016. Main aim of this SIG: to write standards/recommendations that the EEBA Committee could then circulate among the members, and also to furnish informed comment to external agencies whenever such possibilities arise. In addition, to write editorials/reviews.
Geographic Reach Europe 
Policy Influence Type Citation in other policy documents
 
Description Regenerative Medicine Expert Group Delivery Sub-Group (House of Lord Science & Technology Committee into Regenerative Medicine)
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description A systematic review of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes
Amount £140,000 (GBP)
Funding ID PB-PG-1215-20037 
Organisation NIHR/HEFCE Higher Education Fund for England 
Sector Public
Country United Kingdom
Start 07/2017 
End 06/2018
 
Description Capacity Building in Higher Education
Amount £700,000 (GBP)
Organisation erasmus + 
Sector Public
Country United Kingdom
Start 10/2017 
End 09/2020
 
Description Cell surface marking of corneal epithelial stem cells: a powerful approach to stem cell enrichment prior to transplantation
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2017 
End 07/2018
 
Description Corneal epithelial stem cell therapy: enhancing safety and stability of cultured product
Amount £120,000 (GBP)
Organisation Yorkshire and Humber Academic Health Science Network 
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 10/2015
 
Description Fund to Support Generation of Data for Patent FMS Newcastle University
Amount £28,600 (GBP)
Organisation University of Newcastle 
Sector Academic/University
Country Australia
Start 11/2014 
End 05/2015
 
Description Health Improvement
Amount £120,000 (GBP)
Funding ID 219 
Organisation Academic Health Science Network for the North East and North Cumbria 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2014 
End 12/2015
 
Description MRC Confidence in Concept
Amount £46,482 (GBP)
Funding ID MC_PC_15030 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2017 
End 06/2017
 
Description MRC project grant
Amount £456,000 (GBP)
Funding ID # MR/S035826/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2018 
End 12/2020
 
Description Morphological and topological image analysis for clinical diagnostics and monitoring of cornea damage
Amount £67,566 (GBP)
Funding ID ST/S002383/1 
Organisation Science and Technologies Facilities Council (STFC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 03/2019
 
Description NIHR Newcastle BRC Support Research Development and Infrastrucutre
Amount £42,100 (GBP)
Funding ID RCF141508 
Organisation National Institute for Health Research 
Department NIHR Newcastle Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 04/2014 
End 03/2016
 
Description NIHR Research for Patient Benefit
Amount £144,908 (GBP)
Funding ID PB-PG-1215-20037 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2017 
End 02/2018
 
Description National Institute of Health Research Newcastle Biomedial Research Centre
Amount £50,000 (GBP)
Organisation National Institute for Health Research 
Department NIHR Newcastle Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 02/2014 
End 02/2015
 
Description Research Capability Funding
Amount £42,111 (GBP)
Funding ID RCF141508 
Organisation Newcastle upon Tyne Hospitals NHS Foundation Trust 
Sector Academic/University
Country United Kingdom
Start 04/2014 
End 03/2016
 
Description Single Cell Genomics Unit
Amount £2,000,000 (GBP)
Funding ID MR/M008886/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2015 
End 12/2015
 
Description Understanding the molecular and cellular complexity of human cornea through single cell analyses
Amount £458,770 (GBP)
Funding ID MR/S035826/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2018 
End 12/2020
 
Title Limbal Stem Cell MACRO Database 
Description Designed a database to collect all relevant clinical information from our phase II clinical trial on ex vivo expansion autologous limbal stem cells for treatment of patients with unilateral limbal stem cell deficiency 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact enormous contribution to data collection that will facilitate data analysis and provide added safety to our clinical trial 
 
Description Assessment of pre-corneal tear film in patients with unilateral total limbal stem cell deficeincy before and after autologous limbal stem cell transplantation. 
Organisation University of Bristol
Department School of Clinical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Assited in original grant application.
Collaborator Contribution The Collaborator will assist to characterize changes in pre-corneal fluid before and after stem cell transplantation for the treatment of unilateral total limbal stem cell deficeincy.
Impact No output yet as this component of the project is due to start in the new year.
Start Year 2017
 
Description Collaboration with Chiesi Farmaceutici SpA, Parma, Italy to develop cell therapy to treat limbal stem cell deficiency 
Organisation Chiesi
Country Italy 
Sector Private 
PI Contribution Setup a clinical trial and a registry with Chiesi using cell therapy to treat patients with unilateral and bilateral limbal stem cell deficiency
Collaborator Contribution Provide the IMP, clinical protocol and financial support.
Impact Setup a clinical trial and registry to treat patients with limbal stem cell deficiency using autologous cell therapy.
Start Year 2020
 
Description Collaboration with Dr Julie Glanville on a NIHR grant application to the Research for Patient Benefit Programme on: "A systematic literature review and meta-analysis of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes" 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution Writing a joint grant application to the NIHR RfPB Programme on: "A systematic literature review and meta-analysis of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes".
Collaborator Contribution As above
Impact NIHR Grant Application submission deadline: 15 March 2016.
Start Year 2017
 
Description Collaboration with Dr Ruby Shalom-Feuerstein, Rappaport Faculty of Medicine of the Technion, Haifa, israel on a grabt application to BIRAX Third Call for Proposal (Deadline 12 May 2016) 
Organisation Technion - Israel Institute of Technology
Department Ruth and Bruce Rappaport Faculty of Medicine
Country Israel 
Sector Academic/University 
PI Contribution Professor Majlinda Lako has been working together with Professor Figueiredo and Dr Ruby Shalom-Feuerstein on a grant application to BIRAX 3rd Call for a collaborative research proposal looking at limbal stem cell heterogeneity.
Collaborator Contribution Jointly writng a grant proposal to BIRAX 3rd Call (Deadline: 12 May 2016).
Impact Writing grant application to BIRAX 3rd call (deadline 12 May 2016).
Start Year 2017
 
Description Cryopreservation of cultured human limbal epithelium 
Organisation Flinders University
Department Ophthalmology
Country Australia 
Sector Academic/University 
PI Contribution Optimization of a protocol for cryopreservation of human limbal epithelial cell cultures based on cell survival. The development of appropriate assays to determine the survival of cells after freezing and thawing are crucial to the successful outcome of the project. In addition to investigate potentially harmful effects of cryoprotectants on Limbal Stem Cells in the absence of freezing and to determine the optimum cooling and warming rates.
Collaborator Contribution The Collaborator is an internatinally known expert in cryobiology, he has been instrumental in setting up the projectThe Collaborator will assist on analysis and interpretation of Quality of Life instruments including the NEI-VFQ25 quality of vision subscale and pain/visual impairment scores. The Collaborator will assist to characterize changes in pre-corneal fluid before and after stem cell transplantation in patients with unilateral total limbal stem cell deficiency.
Impact We have just started this project 6 months ago therefore not in a position to report any substantive outcome yet.
Start Year 2015
 
Description Cryopreservation of cultured human limbal epithelium 
Organisation University of Bristol
Department School of Clinical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Optimization of a protocol for cryopreservation of human limbal epithelial cell cultures based on cell survival. The development of appropriate assays to determine the survival of cells after freezing and thawing are crucial to the successful outcome of the project. In addition to investigate potentially harmful effects of cryoprotectants on Limbal Stem Cells in the absence of freezing and to determine the optimum cooling and warming rates.
Collaborator Contribution The Collaborator is an internatinally known expert in cryobiology, he has been instrumental in setting up the projectThe Collaborator will assist on analysis and interpretation of Quality of Life instruments including the NEI-VFQ25 quality of vision subscale and pain/visual impairment scores. The Collaborator will assist to characterize changes in pre-corneal fluid before and after stem cell transplantation in patients with unilateral total limbal stem cell deficiency.
Impact We have just started this project 6 months ago therefore not in a position to report any substantive outcome yet.
Start Year 2015
 
Description Cryopreservation of cultured human limbal epithelium 
Organisation University of Bristol
Department School of Clinical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Optimization of a protocol for cryopreservation of human limbal epithelial cell cultures based on cell survival. The development of appropriate assays to determine the survival of cells after freezing and thawing are crucial to the successful outcome of the project. In addition to investigate potentially harmful effects of cryoprotectants on Limbal Stem Cells in the absence of freezing and to determine the optimum cooling and warming rates.
Collaborator Contribution The Collaborator is an internatinally known expert in cryobiology, he has been instrumental in setting up the projectThe Collaborator will assist on analysis and interpretation of Quality of Life instruments including the NEI-VFQ25 quality of vision subscale and pain/visual impairment scores. The Collaborator will assist to characterize changes in pre-corneal fluid before and after stem cell transplantation in patients with unilateral total limbal stem cell deficiency.
Impact We have just started this project 6 months ago therefore not in a position to report any substantive outcome yet.
Start Year 2015
 
Description Investigatigation of increased incidence of "Acid Attacks" in Newcastle upon Tyne 
Organisation Northumbria Police
Country United Kingdom 
Sector Public 
PI Contribution I have instigated this collaboration with Northumbria Police to investigate the increased incidence of "Acid Attacks" in Newcastle upon Tyne over the last 5 years. This initiative has shown an increased incidence of more than doubled over the last 4 years. We are currently setting up a more extensive collaboration in our region trying to understand the problem and also to develop initiatives to prevent such events.
Collaborator Contribution Northumbria Police has investigated form the Police point of view what has been the numbers of "Acid Attacks" over the last 4 years and has shown similarly increased numbers. Northumbria Police and I are currently setting up a more extensive collaboration in our region trying to understand the problem and also to develop initiatives to prevent such events.
Impact We have been able to determine the increasd incidence of " Acid Attacks" in our region and are currently establishing furtherr collabroation with ASTI (Acid SurvivorsTrust International) cahrity, based in London setting up a joint programme aiming to "Early prevention: acid violence reduction and changing attitude in teh communit".
Start Year 2018
 
Description Investigation of inflammatory and immune cell biomarkers on superficial keratotomy tissue excised at the time of ex vivo expanded autologous limbal stem cell transplantation in patients with unilateral total limbal stem cell deficiency 
Organisation Newcastle University
Department Institute of Cellular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Involved in concept, design and methodology of the project; but also data analysis and interpretation of findings.
Collaborator Contribution Professor Simi Ali will perform the immunostaining, microarray and elisa based analysis for inflamatory and immune markers
Impact Still collecting samples (n=7). Due to start project in the new year.
Start Year 2016
 
Description Pilot Project to investigate the migration of limbal stem cells. 
Organisation Loughborough University
Department Wolfson School of Mechanical and Manufacturing Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Involved in concept, design and methodology of the project; but also data analysis and interpretation of findings.
Collaborator Contribution The project will centre around the development of optical systems to track the migration of corneal epithelial stem cells and a statistical model to describe the behaviour, with an eventual aim of developing techniques for stimulating increased healing post-wounding and transplantation.
Impact We are in the preliminary stages of the project where Prof Wildman is characterising the culture growth so that we can approximate the rate at which the culture develops and then use this information to design subsequent experiments.
Start Year 2012
 
Description Quality of Life analysis of limbal stem cell transplantation for the treatment of total unilateral limbal stem cell deficiency. 
Organisation Flinders University
Department Ophthalmology
Country Australia 
Sector Academic/University 
PI Contribution The collaborator wil asssit on data anlysis and interpretation of quality of life questionnaires, inclusing NEI-VFQ25 quality of vision subscale and pain/visual impairment scores
Collaborator Contribution The Collaborator will assist on data analysis and interpretation of Quality of Life Questionnaires, inlcuding NEI-VFQ25 quality of vision subscale and pain/visual impairment scores
Impact No output yet as this part of the project is due to start in the new year.
Start Year 2017
 
Description The use of new animal origin-free cell culture suplements known as HKSdaFREE, HKGE2, HEGE and CRYOVIVE for LSC culture 
Organisation Avan Biotech
Country Canada 
Sector Private 
PI Contribution We are currently growing ex vivo limbal stem cells (LSC) using the above animal-free culture medium to compare with our normal epithelial medium.
Collaborator Contribution The aim is to potentially use a better clinical grade/animal free culture medium that will be commercially availble to grow limbal stem cells for transplantation.
Impact The collaboration is at an early stage and there is no output yet.
Start Year 2011
 
Description Transplantation of hESC/hiPSC derived corneal epithelial cells in immunocompromised recipients 
Organisation University College London
Department Department of Haematology
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed in Newcastle the hESC/hiPSC derived corneal epithelial cells
Collaborator Contribution The hESC/hiPSC derived corneal epithelial cells has been transplanted to immunocompromised recipients
Impact Collaboration still in progress.
Start Year 2017
 
Description collaboration with Dr. Tor Utheim's group, Norway 
Organisation University of Oslo
Country Norway 
Sector Academic/University 
PI Contribution We are sharing with Dr. Utheim's group our culture system for the ex vivo expansion of LSCs on human amniotic membrane.
Collaborator Contribution Dr.Utheim's team is sharing data with our group with regard to transport conditions for limbal biopsies as well as ex vivo cultured LSCs.
Impact not yet
Start Year 2019
 
Title Expansion method 
Description A method for expansion of limbal stem cells comprises: (i) providing a limbal biopsy on a human amniotic membrane; (ii) culturing for a first time period the limbal biopsy in the presence of epithelial culture medium comprising hydrocortisone, insulin, tri-iodothyronine, adenine, and epidermal growth factor, wherein the epithelial culture medium is supplemented with serum and one or more antibiotics; and (iii) substituting the epithelial culture medium of step ii) with epithelial culture medium comprising hydrocortisone, insulin, tri-iodothyronine, adenine, and epidermal growth factor, wherein the epithelial culture medium is supplemented with serum and is free from antibiotics, and culturing for a second time period; wherein the expanded limbal stem cells form an epithelial sheet on the human amniotic membrane and wherein the serum is derived from the same donor as the limbal biopsy. A defined epithelial culture medium comprising hydrocortisone, insulin, tri-iodothyronine, adenine, and epidermal growth factor, and optionally cholera toxin is provided for use in such a method; the culture medium may be supplemented with penicillin and/or streptomycin for use in step (ii) of the method. 
IP Reference GB2531492 
Protection Patent application published
Year Protection Granted 2016
Licensed No
Impact optimised method for ex vivo expansion of limbal stem cells
 
Title Limbal Stem cell graft manufacture methods (Narrow); University of Newcastle upon Tyne; #SL104# 
Description This patent describes our method of ex vivo expansion of limbal stem cells on human amniotic membrane. 
IP Reference NL/P213205GB 
Protection Patent application published
Year Protection Granted 2014
Licensed No
Impact no impacts yet
 
Title Oral Mucosa in Limbal Stem Cell Deficiency; University of Newcastle upon Tyne; #SL104# 
Description This patent describes the culture method for the ex vivo expansion of oral mucosa epithelial cells on human amniotic membrane. 
IP Reference KLT/P210577GB 
Protection Patent application published
Year Protection Granted 2014
Licensed No
Impact no impacts yet
 
Title Efficacy and Safety of Autologous Cultivated Limbal Stem Cells Transplantation (HOLOCLAR) 
Description The purpose of this trial is to confirm the efficacy and Safety of Holoclar (Autologous Cultivated Limbal Stem Cells Transplantation) at one year after the first treatment. Completed recruitment (end 2018). This trial is sponsored by Chiesi Farmaceutici S.p.A. 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Wide-scale adoption
Year Development Stage Completed 2019
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Holoclar is the first stem cell medicinal product and has been approved by NICE. Since Holoclar has been granted a conditional approval this trial will provide data on the benefits and risks of Holoclar from a prospective clinical trial. 
URL https://clinicaltrials.gov/show/NCT02577861
 
Title Ex vivo Expansion of Autologous Limbal Stem Cell for Transplantation in Patients with Unilateral Limbal Stem Cell Deficiency 
Description Phase II clinical Trial to evaluate the long-term safety and efficacy of Transplantation of an animal-free, GMP compliant, cultivated autologous limbal epithelial stem cells on human amniotic membrane (HAM) for treatment of patients with unilateral total limbal stem cell deficiency (LSCD). 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2012
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Phase I study has demonstrated an improvement in patient QoL with consequent Improvement in patient care using an animal free cell culture technique. Currently engaged in a Phase II study to demonstrate its safety and efficacy. 
URL http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=11185
 
Description Core member of committee C, BBSRC 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact member of committee C: reading and reviewing proposals, helping to shape UK policy
Year(s) Of Engagement Activity 2017,2018,2019
 
Description 113th Deutsche Ophthalmologishche Gesellschaft (DOG) Annual Congress. 1st October 2015. Estrel Conference Centre, Berlin, Germany. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited Internationals speaker on: "Ex vivo expanded autologous OME transplantation for treatment of bilateral total limbal stem cell deficiency". The talk generated an enormous interest and debate on availability of cell therapy to treat unilateral and bilateral limbal stem cell deficiency. We are setting up a potential collaboration on limbal stem cell research with Professor Daniel Meller from Jena, Germany
Year(s) Of Engagement Activity 2015
 
Description 6th EU Cornea. 4-5 September 2015. Barcelona, Sapin. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Giving a talk to a mixture of clinical and research scientists audience with main interest in cell therapy to treat limbal stem cell deficiency. The talk generated excellent discussion on the subject of "Stem cell transplantation in bilateral limbal deficiency", with special interest in our primary research on ex vivo expanded autologous oral mucosa epithelium to treat patients with bilateral stem cell deficiency.
Year(s) Of Engagement Activity 2015
 
Description 7th EU Cornea Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact EU Cornea special symposium on limbal stem cells
Year(s) Of Engagement Activity 2016
 
Description Acute Chemical Injury - Presentation, Management & Complications 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker at the Swiss Society of Ophthalmology Congress. Interlaken, Switzerland, August 2019.
Year(s) Of Engagement Activity 2019
 
Description Advisory Board Holoclar 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Advisory board (International experts in limbal stem cell therapy) on the use of Holoclar
Year(s) Of Engagement Activity 2018,2019
 
Description Amniotic Mebrane in Ocular Surface Reconstruction - Use or Abuse? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker at the Royal College of Ophthalmology Annual Congress Annual Congress, Cornea & Ocular Surface Day. 23rd May 2019, Glasgow, UK.
Year(s) Of Engagement Activity 2019
 
Description Association for Research in Vision and Ophthalmology (ARVO) Annual meeting, Denver, Colorado, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented a talk on "Patient reported outcomes before and following ex vivo cultured autologous limbal stem cell transplantation for total unilateral limbal stem cell deficiency". This generated a lot of discussions and further collaboration with Professor Konrad Pesudovs from Flinders University, Australia.
Year(s) Of Engagement Activity 2015
 
Description Developments in Limbal Stem Cell Transplantation - invite speaker at the 44th Trends in Ophthalmology 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact It is an international 2 days Conference highlighting current trends and pearl in Ophthalmology. In excess of 200 delegates attended on both days of the event. 95% of the delegates thought the meeting overall was very good to excellent.
Year(s) Of Engagement Activity 2019
URL http://www.eyehope.co.uk
 
Description European Commission, Evaluator of REA-FET-OPEN-2017 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact panel member: discuss proposals and reach funding decisions
Year(s) Of Engagement Activity 2017,2018,2019
 
Description European Commission, Member of H02020 panel "Clinical Research on regenerative medicine", June 2017 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact panel member: proposal discussion and selection for funding
Year(s) Of Engagement Activity 2017,2018,2019
 
Description Genetics Matter Day 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Around 100 members of the public attend the Genetics Matter Day organised by the Institute of Genetic Medicine each year. Prof. Lako's group organises an "eye table" stimulating discussion on eye diseases and stem cell treatments.
Year(s) Of Engagement Activity 2015,2016
 
Description Human Cloning and Stem Cell research Through the Medium of Law 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact My presentation generated a lot of thinking and discussions regarding visual impairment, stem cell research, stem cell application in humans, rare diseases

After my talk students asked if they could visit the stem cell laboratory
Year(s) Of Engagement Activity 2014
 
Description Invited Speaker at the MipTec 2014 - The Leading European Event for Drug Discovery 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Following Prof. Lako's talk in this conference, a new collaboration is being set up with Roche Pharmauceticals.

An exchange scheme for postdoctoral scientists between Lako's lab and Roche is being set up following the talk in this conference.
Year(s) Of Engagement Activity 2014
 
Description Invited panellist of the European Opthalmology Futures Forum, London 11th September 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Prof. Lako was part of the panel describing the impact of gene and stem cell therapy for treatment of blindness.

press release plus publication
Year(s) Of Engagement Activity 2014
 
Description Limbal stem cell (HOLOCLAR) European Advisory Board Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The advisory Board was composed of experts in the field of limbal stem cell diseases from Europe and USA. The main purpose of this AB is meet once a year to discuss current and future treatment options for patients with limbal stem cell deficiency (LSCD) including HOLOCLAR. This included patients with unilateral and bilateral, moderate to severe LSCD secondary to chemical burns.
Year(s) Of Engagement Activity 2017
 
Description Limbal stem cell therapy - EU market authorisation license 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Workshop discussion at the Society of Legal Scholars Annual Seminar 2015 - Incentivising Innovation and Higher Standards in Regulations and Liability Relating to Medicines - 25th March 2015. Durham University, Durham, UK. This led to a collaboration with Professor Shaun Pattinson, Chair of Medical Law and Ethics & Deputy Head of Durham Law School.
Year(s) Of Engagement Activity 2015
 
Description Long-term Treatment: Developments in Limbal Stem Cell Transplantation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker at the Swiss Society of Ophthalmology Congress. Interlaken, Switzerland, August 2019.
Year(s) Of Engagement Activity 2019
 
Description Member of the H2020-JTI-IMI2-panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Ho2020 panel member: proposal discussion and funding, helping to share EU research policy and funding.
Year(s) Of Engagement Activity 2017,2018
 
Description Member of the H2020: SC1-BHC-09-2018 panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Ho2020 panel member: proposal discussion and funding, helping to share EU research policy and funding.
Year(s) Of Engagement Activity 2006,2017
 
Description NHSBT Tissue & Eye Services Annual Review Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I was invited to give a talk on "Amniotic Membrane Transplantation in Ophthalmology, including limbal stem cell deficiency" at the NHSBT Tissue & Eye Services Annual Review Day in Liverpool, UK. The audience consisted of national members of NHSBT Tissue and Eye Services. It was a very interactive meeting including discussions on future collaborations in areas of common research interest.
Year(s) Of Engagement Activity 2018
 
Description Nordic Ophthalmological Conference, Aarhus, Denmark 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Special session of the Nordic Ophthalmological Conference on stem cells/regenerative medicine
Year(s) Of Engagement Activity 2016
 
Description Ocular Burns Patients: Where do they Come from? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker at the "Limbal Stem Cell Deficiency due to Ocular Burns: The Patient's Journey" Symposium at the EU Cornea 2019. 13 September 2019. Paris, France. (also chaired the Symposium).
Year(s) Of Engagement Activity 2019
 
Description Ocular Surface Inflammation & angiogenesis in Limbal Stem Cell Deficiency 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker at Linkoping University, in May 2019; Linkoping, Sweden as part of a PhD viva examination as external examiner. This initiative/interaction has resulted in additional collaborations in the field of limbal stem cell deficiency (COST Action CA18116 ANIRIDIA-NET Action Title: Aniridia: networking to address an unmet medical, scientific, and societal challenge)
Year(s) Of Engagement Activity 2019
 
Description Presentation at EU Cornea Limbal Stem Cell Symposium in Amsterdam 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact 60 ophthalmologists form around the world attended this symposium on limbal tem cells. I gave a talk on: Limbal Stem Cell Culture: Explant vs. Dissociated Cells.

Opportunity to discuss potential collaborations with stem cell colleagues from Europe. In particular on cell shipment.
Year(s) Of Engagement Activity 2013
URL http://www.eucornea.org
 
Description Public debate: "Future of Stem Cell Debate". Invited panellist 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 200 people attended the debate. They were very active and asked a number of questions throughout the whole debate.

Increased public awareness of our research project. This initiative generated more interest in the project that was followed by a number of emails from the public.
Year(s) Of Engagement Activity 2010
 
Description Regenerative Medicine Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact around 300 people attended the talk
location: Skopje/Macedonia, March 2011

the talk raised interest amongst opthalmic clinicians and a few biotech companies with respect to cryopreservation of corneal epithelial stem cells
Year(s) Of Engagement Activity 2011
 
Description Regenerative medicine - stem cells, genetic engineering and biotechnology" Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact 200 people attended the talk
location Bosnia Herzegovina-Banja Luka, 21st september 2012

The talk raised high interest amongst the opthalmic clinicians and we have received a number of invitations to collaborate
Year(s) Of Engagement Activity 2012
 
Description Visit to the Department of Ophthalmology and Research Laboratory, University Hospitals of Geneva, Switzerland. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact This visit to the Department of Ophthalmology and the Research Laboratory of Department of Clinical Neurosciences, University Hospitals of Geneva, Switzerland. 4 - 6 March 2013. I had the opportunity to give a talk on the Limbal Stem Cell research Project to Ophthalmologists and scientists (50 people).

Established strong links with the department and currently exploring potential research collaboration.
Year(s) Of Engagement Activity 2013
 
Description Visiting Professor to Federal University of Pernambuco, Recife, Brazil. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact This visit to Department of Ophthalmology and the Laboratory of Immunopathology Keizo Asami (LIKA), Recife, Pernambuco, Brazil, 18 - 20 March 2013. I had the opportunity to give 2 talks on the Limbal Stem Cell research Project: 1. to Ophthalmologists and scientists at the Federal University of Pernambuco (50 people) and 2. at the XIX Norte-Nordeste Ophthalmology Congress (800 people). 21 -23 March 2013. Recife, Brazil.

Contacts have been established with potential for future collaborations and interchange of scientists visiting our labs or even to engage in a higher degree.
Year(s) Of Engagement Activity 2013
 
Description XXIX Annual Meeting of the European Eye Bank Association. 19-21 January 2017. Prague, Czech Republic. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact SIG on Regenerative Medicine
Year(s) Of Engagement Activity 2017
 
Description XXVIII Annual Meeting of the European Eye Bank Association. 22-23 January 2016. Aarhus, Denmark. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker to give a talk on: Molecular analysis of inflammation in corneal pannus tissue from patients with total limbal stem cell deficiency by quantitative real time PCR". Since then I have been invited to be a member of the European Eye Bank Association Special Interest Group on Limbal Stem Cells.
Year(s) Of Engagement Activity 2015
 
Description national limbal stem cell workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dr. Bojic from Lako and Figueiredo group attended the workshop and presented our work.
Year(s) Of Engagement Activity 2015