Evidence map›Paper›PMID 28940313›Full record

ArticleXenotransplantation2017

N-glycolylneuraminic acid knockout reduces erythrocyte sequestration and thromboxane elaboration in an ex vivo pig-to-human xenoperfusion model.

Arielle Cimeno, Wessam Hassanein, Beth M French, Jessica M Powell, Lars Burdorf, Olga Goloubeva, Xiangfei Cheng, Dawn M Parsell, Jagdeece Ramsoondar, Kasinath Kuravi and 13 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Xenotransplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  7. Profiling HumanBiology · 2021
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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

23 authors at 2 institutions in 1 country.

Arielle CimenoDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-8179-2569
Wessam HassaneinDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Beth M FrenchDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-6493-318X
Jessica M PowellDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Lars BurdorfDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Olga GoloubevaDepartment of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Xiangfei ChengDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Dawn M ParsellDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Jagdeece RamsoondarRevivicor Inc., Blacksburg, VA, USA.
Kasinath KuraviRevivicor Inc., Blacksburg, VA, USA.
Todd VaughtRevivicor Inc., Blacksburg, VA, USA.
Mehmet C UluerDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Emily ReddingDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Natalie O'NeillDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Christopher LairdDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Alena HershfeldDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Ivan TatarovDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Kathryn ThomasDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
David AyaresRevivicor Inc., Blacksburg, VA, USA.
Agnes M AzimzadehDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Richard N PiersonDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Rolf N BarthDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
John C LaMattinaDepartment of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
University of Maryland, Baltimore · USVirginia Tech · US

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MOHIUDDIN, MUHAMMAD M · 2010 to 2024
$26.3M
Mechanisms of GalTKO Lung Xenograft InjuryU01AI066335 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI PIERSON, RICHARD N · 2005 to 2009
$2.4M
CRISPR-Modified Cardiac Xenograft TransplantationR01AI153612 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI PIERSON, RICHARD N · 2020 to 2020
$796k
NIAID NIH HHS R01 AI153612NIAID NIH HHS U01 AI066335NIAID NIH HHS U19 AI090959
6 · The paper itself

Abstract

backgroundWild-type pigs express several carbohydrate moieties on their cell surfaces that differ from those expressed by humans. This difference in profile leads to pig tissue cell recognition of human blood cells causing sequestration, in addition to antibody-mediated xenograft injury. One such carbohydrate is N-glycolylneuraminic acid (Neu5Gc), a sialic acid molecule synthesized in pigs but not in humans. Here, we evaluate livers with and without Neu5Gc in an ex vivo liver xeno perfusion model.

methodsLivers from pigs with an α1,3-galactosyl transferase gene knockout (GalTKO) and transgenic for human membrane cofactor (hCD46) with (n = 5) or without (n = 7) an additional Neu5Gc gene knock out (Neu5GcKO) were perfused ex vivo with heparinized whole human blood. A drug regimen consisting of a histamine inhibitor, thromboxane synthase inhibitor, and a murine anti-human GPIb-blocking antibody fragment was given to half of the experiments in each group.

resultsLiver function tests (AST and ALT) were not significantly different between livers with and without the Neu5GcKO. GalTKO.hCD46.Neu5GcKO livers had less erythrocyte sequestration as evidenced by a higher mean hematocrit over time compared to GalTKO.hCD46 livers (P = .0003). The addition of Neu5GcKO did not ameliorate profound thrombocytopenia seen within the first 15 minutes of perfusion. TXB2 was significantly less with the added drug regimen (P = .006) or the presence of Neu5GcKO (P = .017).

conclusionsThe lack of Neu5Gc expression attenuated erythrocyte loss but did not prevent profound early onset thrombocytopenia or platelet activation, although TXB2 levels were decreased in the presence of Neu5GcKO.

Indexed as

Transplantation, HeterologousAnimalsAnimals, Genetically ModifiedGalactosyltransferasesGene Knockout TechniquesGraft SurvivalHeterograftsHumansMembrane Cofactor ProteinNeuraminic AcidsSwineThrombocytopeniaGalactosyltransferasesMembrane Cofactor ProteinN-acetyllactosaminide alpha-1,3-galactosyltransferaseNeuraminic AcidsN-glycolylneuraminic acidex vivo perfusionliver xenotransplantationN-glycolylneuraminic acidsialic acids

Identifiers

PMID28940313
PMCPMC6687465
OpenAlexW2758923917

What OpenQuestion holds

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Registered trials

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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.