Evidence map›Paper›PMID 31984530›Full record

ArticleXenotransplantation2020

Epigenetic biomarkers indicate islet cell death in xenotransplantation.

Christopher Faulk, Kate R Mueller, David Cheishvili, Mathia Colwell, Anne-Sophie Pepin, Moshe Syzf, Bernhard J Hering, Christopher Burlak

Open access · greenAbstract read
In one paragraph

Article in Xenotransplantation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 50% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Christopher FaulkDepartment of Animal Sciences, College of Food, Agricultural and Natural Resource Sciences, University of Minnesota, Saint Paul, MN, USA.ORCID 0000-0002-9749-9658
Kate R MuellerDepartment of Surgery, Schulze Diabetes Institute, School of Medicine, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0002-8638-365X
David CheishviliDepartment of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada.
Mathia ColwellDepartment of Animal Sciences, College of Food, Agricultural and Natural Resource Sciences, University of Minnesota, Saint Paul, MN, USA.
Anne-Sophie PepinDepartment of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada.
Moshe SyzfDepartment of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada.
Bernhard J HeringDepartment of Surgery, Schulze Diabetes Institute, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
Christopher BurlakDepartment of Surgery, Schulze Diabetes Institute, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
University of Minnesota · USMcGill University · CA

Funding

Pig-to-Monkey Islet XenotransplantationU01AI120130 · NIAID · UNIVERSITY OF MINNESOTA · PI GRAHAM, MELANIE LYNN, HERING, BERNHARD JOSEF · 2015 to 2019
$5.6M
The Environment and Epigenome: Interplay of Toxicants and Transposons in MammalsR00ES022221 · NIEHS · UNIVERSITY OF MINNESOTA · PI FAULK, CHRISTOPHER · 2015 to 2017
$728k
The Environment and Epigenome: Interplay of Toxicants and Transposons in MammalsK99ES022221 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FAULK, CHRISTOPHER · 2013 to 2014
$180k
NIAID NIH HHS U01 AI120130NIEHS NIH HHS K99 ES022221NIEHS NIH HHS R00 ES022221
6 · The paper itself

Abstract

backgroundXenotransplantation of porcine islets has emerged in recent decades as a potential treatment for type 1 diabetes (T1D). Current methods of detection, indicative of successful engraftment, occur downstream of actual islet death. Epigenetic biomarkers can be detected in circulating cell-free DNA (cfDNA) to provide an earlier indication of graft dysfunction.

aimsThe present study identified a biomarker of islet death using differential methylation of the insulin gene, INS, originating from β-cells in porcine islets. MATERIALS &

methodsPyrosequencing primers specific for porcine INS were designed to quantify hypomethylation along 12 cysteine-guanine dinucleotide (CpG) sites, including three sites in the cyclic adenosine monophosphate (cAMP) response element (CRE) binding protein 2 (CRE2) binding region of the 5' untranslated region (UTR) and nine sites within intron 2.

resultsPCR amplification of bisulfite-converted DNA combined with pyrosequencing data support the conclusion that hypomethylated porcine INS is specific to islet origin.

conclusionMoreover, the results of this study indicate a highly specific epigenetic biomarker, capable of detecting a single islet, supporting the measurement of cfDNA as a biomarker for transplanted islet death. Defining the epigenetic characteristics of porcine-derived islets within cfDNA will be crucial to develop a better understanding of graft survival immunology for transplantation.

Indexed as

Islets of Langerhans TransplantationTransplantation, HeterologousAnimalsBiomarkersDiabetes Mellitus, Type 1Epigenesis, GeneticFemaleGraft SurvivalHeterograftsInsulinInsulin-Secreting CellsIslets of LangerhansMaleSwineBiomarkersInsulinDNA methylationepigenetic biomarkerhistone methylationhypomethylationINSinsulinPorcine isletsxenotransplantationβ-cells

Identifiers

PMID31984530
PMCPMC7162715
OpenAlexW3003551095

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.