VISICORT clinical trial takes its first steps

VISICORT celebrates its first validation shipment of Stromal Cells from CCMI Galway to Charité Research Organisation (CRO) in Berlin for the commencement of the VISICORT clinical trial.

In the pictures below, Aoife Duffy, Manufacturing Manager at Centre for Cell Manufacturing Ireland (CCMI) at the National University of Ireland Galway is holding the first cell shipment. Cells were manufactured by CCMI in Galway and transport was performed by Biostór Ireland – a “Known Shipper” with the Irish Aviation Authority (IAA). This is the first of 7 shipments to be carried out during 2018 to establish the safety and tolerability of two intravenous infusions of allogeneic human bone marrow-derived mesenchymal stromal cells (allogenic-BM-MSC) and evaluate the potential efficacy of pre-transplant intravenous infusions of allogenic-BM-MSC to reduce the risk of acute rejection of corneal re-transplants.

As a Known Consignor, Biostór can ship cells without the use of X-ray scans. All air cargo and truck shipments are now subject to X-Ray scan. X-rays would be hazardous to the MSCs. Becoming “Known” involved Garda Vetting, the completion of a 1-day of Aviation Security Training course, writing a comprehensive Air Cargo Security Manual and SOPs, and a site audit by IAA.

Biostór’s Peadar MacGabhann comments, “Becoming a Known Consignor with the IAA was worth it and ensures that Biostór can support future VISICORT cell therapy trials and ensure the project reaches the conclusions that were planned at the outset. how this will impact the project.”

Feature image photo credit: Wellcome Collection with a Creative Commons 4.0 International license

VISICORT celebrates International Clinical Trials Day with the HRB-TMRN

EU funded projects VISICORT, ADIPOA-2AUTOSTEM and NEPHSTROM coordinated by the Regenerative Medicine Institute (REMEDI) at National University of Ireland, Galway exhibited at a unique outreach activity targeted at primary school students. The event called the START competition was the brainchild of the Health Research Board (Ireland)’s Trials Methodology Research Network (HRB-TMRN) in Galway. In celebration of International Clinical Trials Day and to draw attention to clinical research conducted in Ireland, young people were invited to design, conduct and report on a randomized clinical trial. On May 18, 2018, three of the short-listed schools assembled at the University in Galway to visit interactive exhibitions, talk with researchers, perform mini-experiments, take part in lively science demonstrations and collect their prizes. The winning school was St. Joseph’s National School from Kinvara, County Galway.

Special thanks to Dr Siobhan Gaughan who organized the stand, Georgina Shaw who prepared the stem cell plates and to NUI Galway volunteers Dr Tina Harte, Dr Cathal Ó Flatharta, Dr. Nahidul Islam, Hannah Egan, Niamh Leonard, Dr. Emily Growney Kalaf, Claire Dooley and Dulan Hasantha Jayasooriya who volunteered their time to work with the young people on behalf of the EU funded project, STEM promotion.  The STEMinator cards used at the exhibition were designed by Cúram, NUI Galway. Also thank you to Lauren, Alibhe and Charlotte for creating the stem cell models.

Read more about the START competition here.

VISICORT attracts attention at ARVO 2018, Honolulu

PI Dr Jesper Hjortdal (right) and Henrik Sejersen (left), Clinical Optometrist at the University Hospital Aarhus in Denmark presented VISICORT at the ARVO 2018 conference. The Association for Research in Vision and Ophthalmology (ARVO) meeting was held from 29 April – 3 May in Honolulu, Hawaii USA. This year’s theme was ‘Imaging in the Eye’. The VISICORT study was titled “Comparison of DMEK and DSAEK in high and low risk posterior lamellar keratoplasty”.

Jesper comments: “Our poster confirmed that on average, patients treated with DMEK obtain better visual acuity than patients treated with DSAEK, but that early re-operations are much more common. An interesting finding was that DMEK grafts had higher endothelial cell density after surgery than DSAEK grafts. In relation to high- and low-risk grafts, failures were similar in patients treated with DMEK/DSAEK.”
“The interest in the topic was very good, and many look very much forward to see results from the main focus of VISICORT: Immunological profiling of patients in keratoplasty.”

ARVO is the largest and most respected eye and vision research organization in the world. With nearly 12,000 researchers as members from over 75 countries, ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders. The poster session is very popular as many colleagues pass by and give comments.

 

VISICORT study published in Stem Cells

A VISICORT study was published recently in Stem Cells. The body of research entitled “Inter‐Species Incompatibilities Limit the Immunomodulatory Effect of Human Mesenchymal Stromal Cells in the Rat” by Paul Lohan, Oliver Treacy, Maurice Morcos, Ellen Donohoe, Yvonne O’Donoghue, Aideen E Ryan, Stephen J Elliman, Thomas Ritter and Matthew D Griffin was accepted for publication on 13 April 2018.

Abstract:

Mesenchymal stem/stromal cells (MSC) are an immunomodulatory cell population which are under pre‐clinical and clinical investigation for a number of inflammatory conditions including transplantation. In this study, a well‐established rat corneal transplantation model was used to test the ability of human MSC to prolong corneal allograft rejection‐free survival using a pre‐transplant intravenous infusion protocol previously shown to be efficacious with allogeneic rat MSC. Surprisingly, pre‐transplant administration of human MSC had no effect on corneal allograft survival. In vitro, human MSC failed to produce nitric oxide and upregulate IDO and, as a consequence, could not suppress rat T‐cell proliferation. Furthermore, human MSC were not activated by rat pro‐inflammatory cytokines. Thus, interspecies incompatibility in cytokine signalling leading to failure of MSC licensing may explain the lack of in vivo efficacy of human MSC in a rat tissue allotransplant model. Inter‐species incompatibilities should be taken into consideration when interpreting pre‐clinical data efficacy data in the context of translation to clinical trial.

VISICORT meets in Wexford, Ireland

The VISICORT consortium was hosted by Biostór Ireland in Wexford on April 26 – 27 2018 for a plenary meeting.

After work package updates were provided, the focus of the meeting became future plans for the remaining months of the project. Discussions focussed on the clinical trial timeline, the publication plans, the future of the VISICORT bio-bank, mechanisms to apply for funding to pursue additional studies, the biomarker analyses, and the “gold mine” of data sets and the potential for clinical and metabolomic studies.

Jesper Hjortdal presents human subject enrolment, follow-up and clinical data analysis.

Agenda VISICORT Wexford April 26 – 27

Prof Ritter presents VISICORT at Cornea and Ocular Surface Biology and Pathology conference

Prof Thomas Ritter, NUI Galway presented Dr Paul Lohan’s VISICORT findings at the Cornea and Ocular Surface Biology and Pathology meeting. The conference was held in Ventura, California from February 18-23 2018. The 2018 conference theme was ‘Defining the Mechanisms Through Which the Cornea, Tear Film and Immune System Operate Under Pathological Conditions’. Thomas’ presentation was titled “Mesenchymal stem cell therapies for efficient treatment of immune-mediated diseases of the eye”.

The Cornea and Ocular Surface Biology and Pathology conference programme can be found here.

 

The 4-stop VISICORT clinical trial monitor tour is complete!

Henrik Sejersen, Clinical Optometrist and VISICORT researcher at the Department of Ophthalmology, University Hospital Aarhus took to the road to visit clinical trial sites undertaking the recruitment and execution of VISICORT’s clinical studies. This VISICORT clinical study monitor tour resulted from a lively discussion at the most recent plenary meeting hosted by the University of Bristol on the 26th and 27th of October 2017. One resulting action item from the meeting entailed visits by Henrik to four clinical trial sites with a view to promoting the completeness and accuracy of clinical data on the cross-sectional and longitudinal studies. Remarking on the tour Henrik stated, “It has been a fantastic trip around Europe; a tight schedule with monitoring visits in 4 different countries in 5 days.  But it was worth the effort. Together with the local investigators, I went through the majority of the prospective and some cross-sectional patients and compared data from their records with the Vims System. In general, the sites have done a good job, but there were some small variations in the way we type in and analyze our results.  That has now been addressed, and the data reliability and accuracy has been increased. Going through that many data I found astounding few mistypes which support the brilliant job the research staff is doing. Each site has now been encouraged to do self-monitoring in the future.”

VISICORT coordinator, Prof. Matthew Griffin of the Regenerative Medicine Institute (REMEDI) at the National University of Ireland, Galway commented: “The VISICORT project is gathering detailed clinical data from new and established corneal transplant recipients at five leading Ophthalmology Centres in Europe. This information will become more and more valuable as time goes by. Of most importance to our research goals, it will allow us to link the molecular signatures in samples taken from the patients early after transplantation to rejection and other harmful events that occur months or years later. We have successfully developed an excellent web-based database that stores this information securely and confidentially. However, accurate and consistent data collection at each site also requires high-level training and dedicated attention to detail from the research teams at each site. Mr Sejersen’s tour of the clinical research sites at Dublin, Bristol, Berlin and Nantes have helped to consolidate the great team spirit that has grown up among the VISICORT researchers involved the project across these sites. This “human touch” element is critical to ensuring that the clinical information gathered throughout the project will be of the highest quality”.

The photos below document the 4-stop tour to the Royal College of Surgeons in Ireland, Dublin, University of Bristol, UK, Charité University Hospital Berlin, and the Institute of Transplantation-Urology- Nephrology at Inserm in Nantes.

Stop one was at the Royal College of Surgeons in Ireland with Diana Malata.

Stop two was at the Department of Clinical Sciences at the University of Bristol with Gemma Brimson.

During stop three at Charité University Hospital Berlin, Henrik reviewed the data with Prof Uwe Pleyer and VISICORT fellow Nina Steinhorst.

 

The last stop was in Nantes at Inserm’s Institute of Transplantation-Urology- Nephrology. Here, Henrik met with Bertrand Favres, and clinical nurses Catherine Ivan and Adeline Chenu.

Peadar Mac Gabhann, Biostór presents the VISICORT concept and best practices

Peadar Mac Gabhann

Peadar Mac Gabhann, Managing Director of Biostór Ireland located in Wexford, Ireland will take VISICORT on the international circuit in 2018 to present the project at several interesting, high profile conferences.

The World Biobanking Summit will be held on the 8th and 9th of March 2018 in Berlin. Peadar presents a case study entitled “Cloud-based Sample Management”. For the entire conference programme, click here.

The 8th annual Biobanking Conference will be held in London on the 13th and 14th of June 2018. The meeting will bring together internationally recognised biorepositories, scientific pioneers from pharmaceutical companies, and academics to strengthen current knowledge in biosample management and their research applications. VISICORT will be presented here. The final programme has not yet been released but for more information, click here.

Finally, Peadar will present ‘VISICORT- a Case Study in Management of a Multi-centre Clinical study in Corneal Transplantation’ at the Biobanking and Regenerative Medicine Congress, 1-2 November 2018 in London. For more information and to register, visit here.

VISICORT publishes in Frontiers in Immunology

The paper ‘Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?’ is based on the work of Dr Paul Lohan, Dr Oliver Treacy, Prof Matthew Griffin, Prof Thomas Ritter and Dr Aideen Ryan of the National University of Ireland Galway. The publication appears in the November 24, 2017, edition of Frontiers in Immunology. This research was funded by VISICORT, amongst other sources. Read the entire manuscript here.

Front. Immunol., 24 November 2017

https://doi.org/10.3389/fimmu.2017.01626

VISICORT researchers exhibit at the largest public science forum in Ireland

VISICORT researchers at NUI Galway exhibited at the Galway Science and Technology Forum on 26 November 2017. In excess of 20,000 people attended the exhibition day. The NUI Galway regenerative medicine stand was the brainchild of Dr Siobhán Gaughan who works across several EU-funded stem cell projects coordinated at NUI Galway. Coordinators Matt Griffin and Thomas Ritter, along with Siobhán Gaughan were on hand to explain the cell research ongoing at the university, the objectives and mission of VISICORT, and to inspire the next generation of stem cell scientists. Several activities were on exhibition.

Microscopes were on hand to display bone marrow-derived MSCs and cells differentiated into fat cells. This display was used as an aid to discuss or explain how we need stem cells in our body to replace dead cells in our body and how these stem cells can differentiate down different pathways to make new fat, bone, skin and muscle.

Anatomical models were exhibited to explain the importance of the three EU-funded clinical trials involving stem cells that currently taking place through the Regenerative Medicine Institute (REMEDI) at NUI Galway:

o VISICORT project aims to treat corneal transplant rejection by using an infusion of human bone marrow-derived stromal cells obtained from healthy bone marrow donors. The cells are expanded in CCMI cell manufacturing facility as a cell product, frozen and shipped to Charite Hospital in Berlin where corneal transplant patients will be treated. The cell therapy used in this trial aims to reduce the risk of rejection of the corneal transplant.

o ADIPOA-2 is treating osteoarthritis using adipose-derived stromal cells. Cells are isolated from fat tissue procured by liposuction, expanded under GMP (good manufacturing practices) conditions in Centre for Cell Manufacturing in Ireland (CCMI), the cell manufacturing facility at NUI Galway and injected into the knee of people with osteoarthritis. The treatment aims to reduce the pain and inflammation.

o NEPHSTROM is a project involving a clinical trial which aims to treat diabetic kidney disease using bone marrow-derived stem cells. Complications of diabetes were explained to help contextualise this project and a diabetic foot model with a black toe was also on hand.

AUTOSTEM is an EU-funded project to develop a robotic clean room platform system for the manufacture of large quantities of cells in bioreactors. These large quantities of therapeutic cells will be required once cell therapy clinical trial results prove successful and a cohort of patients will be line up for treatment worldwide. The AUTOSTEM video ran on a loop for display to the public.

Special thanks to Dr Paul Lohan for tech support with the films and Dr Georgina Shaw for supplying the cells for display. Also thanks to Ning Ge and Yicheng Ding of the iPS cell group at REMEDI led by Prof Sanbing Shen.

For more photos and information about the Galway Science & Technology Festival 2017, follow us on Twitter @VISICORT

For more information on the projects mentioned, please see:

• ADIPOA-2 http://adipoa2.eu/ is led by Prof Frank Barry. Cartilage repair in the knee using stem cells derived from fat.
• VISICORThttp://visicort.eu/ is coordinated by Prof Matthew Griffin. Infusions of bone marrow (BM)- derived stem cells to treat people with corneal transplants avoid transplant rejection.
• NEPHSTROM http://nephstrom.eu/ Led by Prof Tim O’Brien. Infusions of BM-MSCs to treat patients with chronic kidney disease
• AUTOSTEM http://www.autostem2020.eu/ is coordinated by Prof Mary Murphy. This project develops a robotic platform and bioreactor which will grow the many cells required to treat future patients. A model bioreactor was available for demonstration.

Galway Advertiser Science Week 2017