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/

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.

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.

New NEPHSTROM study published in the CCLM

A new NEPHSTROM study has just been published in the Clinical Chemistry and Laboratory Medicine (CCLM): “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)” by Siobhan M. Hamon, Tomás P. Griffin, Md Nahidul Islam, Deirdre Wall, Matthew D. Griffin, and Paula M. O’Shea.

Background: Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine, is a promising biomarker of renal functional decline in diabetic kidney disease (DKD). This study aimed primarily to establish normative data and secondarily to evaluate the potential utility of GDF-15 in DKD using Roche Diagnostics electrochemiluminescence immunoassay (ECLIA) in an Irish Caucasian population.

Methods: Following informed consent, 188 healthy volunteers and 128 participants with diabetes (72 with and 56 without DKD) were recruited to a cross-sectional study. Baseline demographics, anthropometric measurements and laboratory measurements were recorded. Blood for GDF-15 measurement was collected into plain specimen tubes kept at room temperature and processed (centrifugation, separation of serum, freezing at −80 °C) within 1 h of phlebotomy pending batch analyses. Reference intervals were determined using the 2.5th and 97.5th percentiles for serum GDF-15 concentration.

Conclusions: The reference interval for serum GDF-15 in a healthy Irish Caucasian population using Roche Diagnostics ECLIA was established and a preliminary determination of the potential of GDF-15 as a screening test for DKD was made. Further prospective validation with a larger DKD cohort will be required before the cutoff presented here is recommended for clinical use.

Published Online: September 15, 2018 | DOI: https://doi.org/10.1515/cclm-2018-0534

Read the entire NEPHSTROM Publications list here: http://nephstrom.eu/nephstrom-publications/

Nephstrom study published in Immunology & Cell Biology

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 EPNaicker SHanley SASlevin SMEykelenboom JKLowndes NFO’Brien TCeredig RGriffin MD, and Dennedy MC was published on 5 March 2018.

 

Abstract

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]

NEPHSTROM research published 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 NEPHSTROM, amongst other sources. Read the entire manuscript here.

Front. Immunol., 24 November 2017

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