EU funded projects NEPHSTROM, VISICORT, ADIPOA-2, and AUTOSTEM 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.
A National University of Ireland Galway REMEDI-Cúram-NEPHSTROM- funded study ‘Phenotypic and functional heterogeneity of human intermediate monocytes based on HLA-DR expression’ has been recently published in Immunology & Cell Biology. The body of research by Connaughton EP, Naicker S, Hanley SA, Slevin SM, Eykelenboom JK, Lowndes NF, O’Brien T, Ceredig R, Griffin MD, and Dennedy MC was published on 5 March 2018.
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults. DRmid and DRhi IM differentially expressed several proteins including CD62L, CD11a, CX3CR1 and CCR2. Overall, the DRmid IM surface profile more closely resembled that of classical monocytes while DRhi IM were more similar to non-classical. However, in contrast to classical monocytes, DRmid IM migrated weakly to CCL2, had reduced intracellular calcium flux following CCR2 ligation and favored adherence to TNF-α-activated endothelium over transmigration. In lipid uptake assays, DRmid IM demonstrated greater internalization of oxidized and acetylated low density lipoprotein than DRhi IM. In obese compared to non-obese adults, proportions and absolute numbers of DRmid , but not DRhi IM, were increased in blood. The results are consistent with phenotypic and functional heterogeneity within the IM subset that may be of specific relevance to lipoprotein scavenging and metabolic health.
doi: 10.1111/imcb.12032. [Epub ahead of print]
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 NEPHSTROM, amongst other sources. Read the entire manuscript here.
Front. Immunol., 24 November 2017
Our partner Prof Dr Hans-Achim Anders of Ludwig-Maximilians-Universitaet Muenchen has coordinated a new publication in Nature Reviews ‘Disease Primers’ on Chronic Kidney Disease (CKD). Contributing authors are Paola Romagnani, Giuseppe Remuzzi, Richard Glassock, Adeera Levin, Kitty J. Jager, Marcello Tonelli, Ziad Massy, Christoph Wanner and Hans-Joachim Anders.
Abstract: Chronic kidney disease (CKD) is defined by persistent urine abnormalities, structural abnormalities or impaired excretory renal function suggestive of a loss of functional nephrons. The majority of patients with CKD are at risk of accelerated cardiovascular disease and death. For those who progress to end-stage renal disease, the limited accessibility to renal replacement therapy is a problem in many parts of the world. Risk factors for the development and progression of CKD include low nephron number at birth, nephron loss due to increasing age and acute or chronic kidney injuries caused by toxic exposures or diseases (for example, obesity and type 2 diabetes mellitus). The management of patients with CKD is focused on early detection or prevention, treatment of the underlying cause (if possible) to curb progression and attention to secondary processes that contribute to ongoing nephron loss. Blood pressure control, inhibition of the renin-angiotensin system and disease-specific interventions are the cornerstones of therapy. CKD complications such as anaemia, metabolic acidosis and secondary hyperparathyroidism affect cardiovascular health and quality of life and require diagnosis and treatment.
Article number: 17088
Published online 23 November 2017
NEPHSTROM 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. Researchers Matthew Griffin, Cathal O’ Flatharta, Grace Davey, and Nahidul Islam along with Siobhán Gaughan were on hand to explain the cell research ongoing at the university, the objectives and mission of NEPHSTROM, 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:
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.
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.
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.
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 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, please follow us on Twitter @Nephstrom
For more information on the projects mentioned, please see:
NEPHSTROM http://nephstrom.eu/ Led by Prof Tim O’Brien. Infusions of BM-MSCs to treat patients with chronic kidney disease
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.
AUTOSTEM http://www.autostem2020.eu/ is coordinated by Prof Mary Murphy. This project is developing 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
The stromal cell therapy, ORBCEL-M™, developed as part of NEPHSTROM, a European Union Horizon 2020-funded research project, has been approved to begin testing in a randomised, double-blind, and placebo-controlled European clinical trial to treat diabetic kidney disease.
Orbsen’s ORBCEL-M™, a novel highly purified positively-selected stromal cell therapy for diabetic kidney disease, has demonstrated significant improvements in kidney function in pre-clinical models of diabetic kidney disease, which represents a significant step towards preparing this therapy for clinical application.
The pan-European clinical trial is being led by nephrologist, Professor Giuseppe Remuzzi at the Mario Negri Institute in Bergamo, Italy with clinical trial recruitment sites in Italy, Ireland (HRB Clinical Research Facility, Galway), and the UK (University Hospitals Birmingham NHS Foundation Trust, Birmingham and Belfast Health and Social Care Trust, Belfast). The primary aim of the clinical trial is to establish the safety and efficacy of ORBCEL-M™ and to show that important markers of diabetic kidney disease are improved, thereby indicating the safety and efficiency of ORBCEL-M™.
Diabetic kidney disease is the single leading cause of end-stage renal disease in the industrialised world, accounting for 40% of new cases of end-stage renal disease in the US and EU. The five-year mortality rate is 39% – a rate comparable to many cancers.
Professor Timothy O’Brien, Dean of the College of Medicine, Nursing and Health Sciences at National University of Ireland Galway, and NEPHSTROM coordinator, comments: “This approval is a vital step towards the initiation of clinical development of this promising new approach to the treatment of diabetic kidney disease, and patient enrollment will commence this summer.”
The trial successfully secured voluntary harmonisation procedure (VHP) approval in April 2017. The VHP is designed to simplify clinical trials across multiple European member states by providing a centralised application procedure for clinical trial approval.
Matt Griffin has been Professor of Transplant Biology in NUI Galway’s School of Medicine and a Consultant Nephrologist at Galway University Hospitals since July 2008. He qualified in Medicine from University College Cork in 1988 and trained in General Medicine and Nephrology in Cork, Dublin and Mayo Clinic Rochester, USA between 1989 and 1997. He pursued a research fellowship in basic immunology at The University of Chicago before returning to join the Division of Nephrology and Hypertension and the William J von Liebig Transplant Center at Mayo Clinic in 1999 where he was a Consultant Nephrologist specialising in Kidney and Pancreas Transplantation and Associate Professor of Medicine at the Mayo Clinic College of Medicine before returning to Ireland.
His research programme has been funded by the NIH, SFI, HRB and the European Commission and is affiliated with the Regenerative Medicine Institute (REMEDI) and CÚRAM Centre for Research in Medical Devices. His interests include basic and transplant immunology, clinical transplantation and immunosuppression, the pathophysiology of renal injury, diabetic kidney disease and stem cell and therapies. He has authored over 130 peer-reviewed manuscripts.
His educational and professional roles have included Director of Education for the Mayo Clinic Transplant Center, standing member of two NIH study sections, Deputy Editor and Co-Editor-in-Chief of the Journal of the American Society of Nephrology, Chair of the NUI Galway Animal Care Research Ethics Committee and Academic Lead for Final Medical Year Renal/Urology teaching modules. He has been a primary supervisor to over 50 postgraduate students and postdoctoral researchers, many of whom are now academic clinicians and scientists.
NUI Galway Head of School of Medicine, Carmel Malone, MD officially welcomed Matt to the new role on 23 August 2017.
Stephanie Rocks, a student at the Regenerative Medicine Institute at NUI Galway presented her work entitled, ‘The Influence of MSC Products on High Glucose-Induced Pro-Inflammatory Signalling Pathways in Human Kidney Epithelial Cells’ at the Regenerative Medicine Research Symposium held in the Biosciences Building at NUI Galway on 18 August 2017. Stephanie’s project was supervised by NEPHSTROM PI Prof. Matthew Griffin and Dr Nahidul Islam. This summer research project was part of the MSc. Regenerative Medicine, a 12-month taught course coordinated by Dr Linda Howard.
Prof. Griffin commented: “It has been a pleasure to have Stephanie as part of our NEPHSTROM team for the last 5 months. The Regenerative Medicine Masters programme at NUI Galway brings another dimension to our basic and translational research efforts at REMEDI. Each year we are fortunate to have outstanding students with diverse undergraduate backgrounds in science, medicine and engineering gain their first extensive research experiences with mentoring from REMEDI PhD students and post-doctoral researchers. For multi-disciplinary projects such as NEPHSTROM, the participation of skilled and highly motivated Master’s students such as Stephanie allows us to extend the overall scope of laboratory research related to key questions such as MSC mechanism of action.
Dr Howard thanked Prof Griffin and his research group for hosting and training Stephanie during this project. The experience of working in an active research environment is invaluable for early stage researchers as they make decisions about their future career goals. Training the next generation of scientists is a important role for researchers and one that NEPHSTROM scientists have clearly taken to heart. For more information on the course, click here.
Hosted by Leiden University Medical Center, the EU MSC2 2017 meeting in Leiden, NL on September 12th and 13th will assemble twelve EU-funded, mesenchymal stromal cell-focussed consortia. Projects to be presented include: REDDSTAR, REACH, RETHRIM, Stellar, MERLIN, Nephstrom, SCIENCE, VISICORT and Adipoa-2, AUTOSTEM, BOOSTB4, SEPCELL, RESSTORE, and RESPINE. This two day, interactive meeting will be held at the Stadsgehoorzaal Leiden. Three overarching aspects of the EU-MSC2 meeting include: mechanisms of action and potency assays; an interactive panel discussion on product development, and product development and market authorisation in a changing regulatory landscape.
The objectives of the meeting are to:
- Enhance knowledge-sharing between EU research groups working in the mesenchymal stromal cell biology domain
- Engage with European Commission Project Officers and other stakeholders from International Society of Cellular Therapy, stem cell ethicists and the European Medicines Agency (EMA)
- Assemble trans-disciplinary research groups working across the global health spectrum but with a common focus of mesenchymal stromal cell biology
- Bring up-and-coming researchers together for networking purposes, and to explore future consortium building and international funding application opportunities
Expected impacts and outcomes:
- Provide opportunities to develop new mesenchymal stromal cell networks
- Disseminate the findings and challenges between MSC-focussed consortia
- Improve the communication potential of research, outcomes and the value of the research
- Explore potential for new commercial technologies
- Collectively enhance the quality and impact of planned clinical trials
These EU-funded projects are:
- Improving the quality of life for European citizens
- Progressing the clinical translation of MSC research and developments
- Contract/Grant agreement number
- EC contribution
- Starting date
1 May 2015
- NEPHSTROM celebrates UK Kidney Week in Harrogate, UK 28th June 2018
- NEPHSTROM celebrates International Clinical Trials Day with the HRB-TMRN 21st May 2018
- Nephstrom study published in Immunology & Cell Biology 26th March 2018
- NEPHSTROM research published in Frontiers in Immunology 4th January 2018
- ‘Chronic Kidney Disease’- a new Nature Reviews Disease Primer by NEPHSTROM researchers 27th November 2017
- National University of Ireland, Galway
- Academisch Ziekenhuis Leiden – Leids Universitair Medisch Centrum
- Orbsen Therapeutics
- Ludwig-Maximilians-Universitaet Muenchen
- Istituto di Ricerche Farmacologiche Mario Negri
- NHS Blood and Transplant
- University Hospital Birmingham NHS Foundation Trust
- The Belfast Health and Social Care Trust
- Pintail Ltd
- Terumo BCT Europe N.V.
- Azienda Ospedaliera Papa Giovanni XXIII Bergamo