PARTNER NEWS: LUMC constructs the largest stem cell facility for the Netherlands and beyond

NEPHSTROM partner Leiden University Medical Center (LUMC) will begin construction of the largest non-profit stem cell and gene therapy facility in the Netherlands in 2020. This will be one of the largest such facilities in Europe measuring at 4000 square metres. The Leiden facility is called NECSTGEN, the Netherlands Centre for the Clinical advancement of Stem Cell and Gene Therapies. Of particular interest to NEPHSTROM and the diabetes research community, NECSTGEN researchers are working on advancing regenerative medicine breakthroughs, such as insulin-producing cells grown on demand for diabetes patients.

The NECSTGEN is a public-private partnership. Researchers and start-ups will soon be welcomed in Leiden, NL in order to accelerate the application of regenerative medicine therapies. NECSTGEN is in part a collaboration with the Canadian Centre for Commercialisation of Regenerative Medicine (CCRM), who realised a similar facility in Toronto.

Currently, there are limited affordable, non-profit facilities where cell and cell product development for regenerative medical treatments are manufactured at scale.

Congratulations to LUMC and their partners for this great achievement and contribution to the regenerative medicine field!

Read the official press release here.

Regenerative Medicine Network publishes EU-MSC2 meeting report featuring NEPHSTROM

NEPHSTROM results were presented at EU-MSC2,  a bi-annual event, organized by partners Leiden University Medical Center in The Netherlands. The meeting assembles researchers, clinicians and cell product developers working within EU-sponsored research consortia, that focus on mesenchymal stromal cell (MSC) therapy for immune-related disorders and tissue regeneration. EU-MSC2, a much-anticipated event provides excellent opportunities for networking, exploring new funding opportunities and the dissemination of results contributing to MSC knowledge-sharing, research and development.

Dr Norberto Perico, Istituto di Ricerche Farmacologiche Mario Negri presented NEPHSTROM’s clinical trial in his September 5, 2019 talk entitled: MSC in diabetic nephropathy: initial clinical results from the NEPHSTROM trial. 

The comprehensive meeting report prepared by Katerina Apelt, Brigitte Wieles and Melissa van Pel of LUMC was published on April 29th, 2020, by the Regenerative Medicine Network.  Read it here.

NEPHSTROM Publication in PLoS One journal

Congratulations to NEPHSTROM partners at the Centre for Public Health, Queen’s University Belfast, the University Hospitals Birmingham, and the National University of Ireland Galway for their recent review: The impact of chronic kidney disease on developed countries from a health economics perspective: A systematic scoping review published in PLoS ONE.

Sarah Elshahat, Paul Cockwell, Alexander P. Maxwell, Matthew Griffin, Timothy O’Brien, and Ciaran O’Neill are the authors of the study which appears in the March 24, 2020 edition of the open-access journal; PLoS ONE 15(3): e0230512. https://doi.org/10.1371/journal.pone.0230512

 

NEPHSTROM consortium meets January 30, 2020 in Dublin

The NEPHSTROM consortium reached a significant milestone when they held the tenth plenary project meeting in Dublin on January 30th, 2020. The meeting was hosted by Pintail Limited, and coincided with the successful treatment of the final patient to be included in the low dose cohort of the clinical trial and provided an opportunity for the consortium to review the progress made with the project as well as plan for the months ahead.

Three new NEPHSTROM-acknowledged papers

PI Prof Matthew Griffin of the National University of Ireland Galway has recently published three papers acknowledging NEPHSTROM work and funding:

  • Fazekas B and Griffin MD. “Mesenchymal stromal cell-based therapies for acute kidney injury: Progress in the last decade”, Kidney International, In Press, 2020 (Review). 28 January 2020. DOI: https://doi.org/10.1016/j.kint.2019.12.019 Pre-proof available here.
  • Swaminathan S and Griffin MD. Editorial: “Innovative biologics and drugs to target renal inflammation”, Frontiers Renal Pharmacol, In Press, 2020  DOI: 10.3389/fphar.2020.00038 Read the full article here.
  • Negi N and Griffin MD. “Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance”. Stem Cells, In Press, 29 January 2020 (Review). DOI: https://doi.org/10.1002/stem.3151 Download the pdf here.

Congratulations to Matt and his international colleagues!

Read the complete list of NEPHSTROM publications here: http://nephstrom.eu/nephstrom-publications/

Luke Barry joins the NEPHSTROM team at Queen’s University Belfast

Our PI Prof Ciaran O’Neill at Queen’s University Belfast reports that Luke Barry has joined the health economist researchers who are working on NEPHSTROM. Luke joined the Belfast team in November 2019. Welcome, Luke!
Queen’s University Belfast (QUB) is a member of the Russell Group of 24 leading UK research-intensive universities, providing world-class education underpinned by world-class research.

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.