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.”

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 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.

 

NEPHSTROM public exhibition at Galway Science & Technology Festival 2018

NEPHSTROM Scientific Project Manager Dr Grace Davey amongst many other NUI Galway researchers participated at the Galway Science and Technology Festival Exhibition Day on Sunday, 25 November 2018. The interactive NEPHSTROM display in the Bailey Allen Hall of the National University of Ireland Galway exhibited models and props which helped to explain diabetes and its complications and future plans for cell therapy to a general audience. A set of stir tank bioreactors was on display to illustrate the technology required to produce large batches of human bone marrow-derived mesenchymal stromal cells (MSCs) for use as a cell therapy.

 

Pictured above Dr Grace Davey, NUI Galway