NEPHSTROM study published in Scientific Reports

Congratulations to the team of researchers Tomás Patrick Griffin, Md Nahidul Islam, Deirdre Wall, John Ferguson, Damian Gerard Griffin, Matthew Dallas Griffin and Paula M. O’Shea who published a NEPHSTROM-acknowledged study in Scientific Reports.  The open-access paper titled “Plasma dephosphorylated-uncarboxylated Matrix Gla-Protein (dp-ucMGP): reference intervals in Caucasian adults and diabetic kidney disease biomarker potential” can be found in the 5th of December 2019 edition with doi  https://doi.org/10.1038/s41598-019-54762-2. Alternatively, download the pdf here.

“Recent studies suggest a possible association between dephosphorylated-uncarboxylated MGP (dp-ucMGP) and glomerular filtration rate (GFR). This study aimed to establish normative data in an adult Caucasian population and to explore the potential utility of dp-ucMGP in patients with diabetes mellitus (DM) with and without diabetic kidney disease (DKD).”

New NEPHSTROM publication from NUI Galway team

“Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers” authored by Md Nahidul Islam, Tomás P. Griffin, Elizabeth Sander, Stephanie Rocks, Junaid Qazi, Joana Cabral, Jasmin McCaul, Tara McMorrow and Matthew D. Griffin at NUI Galway was published today, the 19th of November 2019. The open-access paper appears in Stem Cell Research & Therapy (2019) 10:329, DOI: 10.1186/s13287-019-1424-5 You can download the pdf here.

Abstract:

Background

Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response.

Methods

Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG) D-glucose or to 5 mM D-glucose + 25 mM D-mannitol (MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4–5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined.

Results

After 72–80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10×) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone.

Conclusions

Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has the potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.

NEPHSTROM PI Prof. Matt Griffin visits leading US medical centre Mayo Clinic to discuss EU-funded mesenchymal stromal cell projects

Prof. Matt Griffin of the National University of Ireland Galway visited the Division of Nephrology and Hypertension and the William J von Liebig Transplant Center at Mayo Clinic, Rochester, Minnesota between September 27th and October 2nd, 2019. While there, he engaged with clinical investigators involved in a range of Mayo Clinic research initiatives in regenerative medicine and transplantation. He gave seminars entitled “Modulating the course of diabetic kidney disease: Are the pieces coming together?” and “Allogeneic MSC in Corneal Re-transplantation: From Pre-clinical Evidence to Regulatory Approval” which focussed on the progress of the NUI Galway-coordinated NEPHSTROM and VISICORT (www.visicort.eu) consortia respectively.

Commenting on the visit, Prof. Griffin, who trained and was a faculty member at Mayo Clinic between 1992 and 2008 said: “There are many shared interests and collaborative links between leading academic centres in the US such as Mayo Clinic and European Commission-funded consortia such as NEPHSTROM and VISICORT. Looking ahead to the next EU research and innovation programme, Horizon Europe, I believe that there will be exciting opportunities to further strengthen these links in the areas of regenerative medicine and cellular therapies for the long-term benefit of people with reduced quality of life due to chronic health conditions.”

NEPHSTROM Coordinator Prof Tim O’Brien wins prestigious Mayo Clinic Distinguished AlumniAward

NEPHSTROM Coordinator Professor Timothy O’Brien, Dean of the College of Medicine, Nursing and Health Sciences at NUI Galway and Consultant Endocrinologist at Galway University Hospitals has received the Mayo Clinic Distinguished Alumni Award. The award was established by the Mayo Clinic Board of Trustees in 1981 to acknowledge and show appreciation for exceptional contributions of Mayo Clinic alumni to the field of medicine.

Professor O’ Brien is an internationally recognised clinician-scientist with expertise in regenerative medicine applied to the treatment of diabetes complications. He has influenced a generation of Irish clinicians and scientists. His ties to Mayo Clinic allow trainees from NUI Galway and Galway University Hospitals to spend time at Mayo Clinic and for Mayo faculty to spend time in the University and hospital in Galway, ensuring that the Mayo Clinic ethos is evident on the wards, and in the clinics and laboratories, in Ireland. He is also a director of the Regenerative Medicine Institute at NUI Galway and is lead endocrinologist at Saolta University Health Care Group and co-director of CÚRAM, the SFI Centre for Research in Medical Devices at NUI Galway.

In addition to his administrative and leadership responsibilities, Professor O’ Brien has a major teaching commitment to the School of Medicine at NUI Galway and was twice awarded the Pat McHugh Medal for Best Consultant Teacher. He maintains a busy clinical practice in general internal medicine, diabetes, endocrinology and metabolism. He established a Bariatric Medicine Clinic in Galway University Hospitals, one of only two such centres in Ireland.

Previously Professor O’ Brien was an endocrinologist at Mayo Clinic in Rochester and an associate professor of medicine at Mayo Clinic College of Medicine and Science.

Read the press release from NUI Galway here.

International Clinical Trials Day 2019 at the CRF Galway

The HRB Clinical Research Facility Galway in Ireland hosted a public event to celebrate International Clinical Trials Day on May 20th 2019. Exhibition stands were on display and informational meetings were held throughout the day to inform the public of all areas of clinical research being undertaken at the facility.

A particular stand was dedicated to the CRF Galway’s stem cell work to inform the public of the cell therapy projects being undertaken with partners within the National University of Ireland Galway and with European partners.  NEPHSTROM was showcased here, as were the related projects VISICORT and ADIPOA-2.

Dr Veronica McInerney comments, “Great interest was expressed in this evolving therapeutic area with approximately 100 members of the public stopping by to hear about what cell therapy involves and to learn about the projects from the clinical researchers on the day.”

Dr Veronica McInerney, CRF Galway

Clinical researchers and visitors, CRF Galway

NUI Galway NEPHSTROM team celebrate 3 recent publications

Congratulations to NEPHSTROM researchers at NUI Galway who have recently published three papers:

“Allogeneic Mesenchymal Stromal Cells (MSCs) are of Comparable Efficacy to Syngeneic MSCs for Therapeutic Revascularization in C57BKSdb/db Mice Despite the Induction of Alloantibody”, A. LiewC. Baustian, D. Thomas, E. VaughanC. Sanz-NoguésM. CreaneX. ChenS. AlagesanP. OwensJ. HoranP. DockeryM. D. GriffinA. DuffyT. O’Brien. Cell Transplant. 2018 Aug;27(8):1210-1221. DOI: 10.1177/0963689718784862. Epub 2018 Jul 17. Download the pdf here.

“Effect of Sodium Glucose Co-Transporter-2 Inhibition on the Aldosterone/Renin Ratio in Type 2 Diabetes Mellitus”, Griffin TP, Islam MN, Blake L, Bell M, Griffin MD, O’Shea PM. Horm Metab Res 2019; 51:91-99. DOI: 10.1055/a-0794-7026. Epub 2018 Dec 6

“Defining reference intervals for a serum growth differentiation factor-15 (GDF-15) assay in a Caucasian population and its potential utility in diabetic kidney disease (DKD)”, Siobhan M. Hamon, Tomás P. Griffin, Md Nahidul Islam, Deirdre Wall, Matthew D. Griffin, Paula M. O’Shea, Clinical Chemistry and Laboratory Medicine (CCLM), 20180534, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, Walter de Gruyter GmbH, Berlin/Boston, 2018, DOI: https://doi.org/10.1515/cclm-2018-0534.

ISPOR 2019 award for NEPHSTROM research

NEPHSTROM-supported research by partners at Queen’s University Belfast and  Belfast Health and Social Care Trust has been identified as a semi-finalist for a Research Poster Presentation Award at ISPOR 2019 in New Orleans, USA. The research poster entitled “PUK21: RACIAL DISPARITIES IN RECORDING ANEMIA AS A COMPLICATION AMONG END-STAGE RENAL DISEASE PATIENTS” will be presented by Nga T.Q. Nguyen on 21 May 2019 at the conference. Nga is a PhD student at Queen’s University Belfast and is supervised by NEPHSTROM PIs Ciaran O’ Neill, Peter Maxwell and Michael Donnelly. At this conference, only the top 10% of accepted research abstracts, based on peer review scoring, are eligible for a research poster award. Congratulations, Nga!

ISPOR is the Professional Society for Health Economics and Outcomes Research founded in 1995 by a small group of dedicated volunteers and visionaries with the goal of serving as a catalyst for advancing the science and practice of health economics and outcomes research worldwide. ISPOR 2019 runs from May 18-22, 2019.

NEPHSTROM consortia hosted by UHBFT in Birmingham

The NEPHSTROM project team recently had another very successful and productive plenary meeting in Birmingham U.K. hosted by NEPHSTROM partner UHBFT. The meeting began with a warm welcome by NEPHSTROM Coordinator Prof Tim O’Brien, NUIG and a roundtable of introductions for any new attendees. In attendance, there were 23 delegates representing NEPHSTROM partner sites. Scientific Programme Manager Dr Grace Davey, NUIG refreshed the team by presenting the project plan and current timelines. Mark Sweetnam from partner Pintail Limited reported on administrative and project management updates including a review of deliverable and milestones and reporting requirements.

After a clinical production update from the GMP manufacturing sites, NEPHSTROM trial sponsor IRFMN updated the group on the latest status of the NEPHSTROM clinical trial. The timelines and plans for the next six months were presented and discussed in detail. Each clinical partner reported on patient recruitment numbers and future plans to do so including additional means to enhance recruitment. At this time the project is in the very exciting phase of patient enrolment and infusion and each site (Italy, U.K. and Ireland) are actively proceeding with administration of the blinded product (NEPHSTROM ORBCEL-M or placebo) to enroled patients. After lunch, QUB provided the team with a summary of what has been accomplished in the last six months and future plans in terms of the health economics aspects of NEPHSTROM. The meeting also included a review of recent dissemination and communication tasks and success stories that have been captured in the media including press releases re the trial and scientific presentations of NEPHSTROM at UK Kidney Week and the American Society of Nephrology meeting in San Diego, USA. The meeting concluded with a round-up of project tasks, publication plans and post-meeting actions.

NEPHSTROM is showcased on the CORDIS website

Journalists from the European Commission have recently reported on NEPHSTROM in order to showcase the project on the CORDIS website. CORDIS is the Community Research and Development Information Service. It is the European Commission’s primary public repository and portal to disseminate information on all EU-funded research projects and their results in the broadest sense.

The CORDIS news piece entitled “Novel therapy for diabetic kidney disease” was published on 3 January 2019 in six languages. The story appears in German, English, Spanish, French, Italian and Polish.

In addition, find the NEPHSTROM factsheet and public reports on the CORDIS website here.