Evidence map›Paper›PMID 30276052›Full record

ArticlePlastic and reconstructive surgery. Global open2018

Ex Vivo Major Histocompatibility Complex I Knockdown Prolongs Rejection-free Allograft Survival.

Jessica B Chang, William J Rifkin, Marc A Soares, April Duckworth, Nakul Rao, Yee Cheng Low, Jonathan P Massie, Piul S Rabbani, Pierre B Saadeh, Daniel J Ceradini

Open access · goldAbstract read
In one paragraph

Article in Plastic and reconstructive surgery. Global open, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. 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

10 authors at 1 institution in 1 country.

Jessica B ChangHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
William J RifkinHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
Marc A SoaresHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
April DuckworthHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
Nakul RaoHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
Yee Cheng LowHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
Jonathan P MassieHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
Piul S RabbaniHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
Pierre B SaadehHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
Daniel J CeradiniHansjörg Wyss Department of Plastic Surgery, New York University Langone Health, New York, N.Y.
NYU Langone Health · US

Funding

Training Program in Stem Cell and Cancer BiologyT32CA160002 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI LEHMANN, RUTH · 2011 to 2015
$1.6M
NCI NIH HHS T32 CA160002
6 · The paper itself

Abstract

backgroundWidespread application of vascularized composite allotransplantation (VCA) is currently limited by the required lifelong systemic immunosuppression and its associated morbidity and mortality. This study evaluated the efficacy of ex vivo (after procurement but before transplantation) engineering of allografts using small interfering RNA to knockdown major histocompatibility complex I (MHC-I) and prolong rejection-free survival.

methodsEndothelial cells (ECs) were transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all in vitro experiments. MHC-I surface expression and knockdown duration were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. After stimulating Lewis recipient cytotoxic lymphocytes (CTL) with allogeneic controls or siMHC-I-silenced ECs, lymphocyte proliferation, CTL-mediated and natural killer-mediated EC lysis were measured. Using an established VCA rat model, allografts were perfused ex vivo with siMHC-I before transplantation. Allografts were analyzed for MHC-I expression and clinical/histologic evidence of rejection.

resultsTreatment with siMHC-I resulted in 80% knockdown of mRNA and 87% reduction in cell surface expression for up to 7 days in vitro (

conclusionsEx vivo siMHC-I engineering can effectively modify allografts and significantly prolong rejection-free allograft survival. This novel approach may help reduce future systemic immunosuppression requirements in VCA recipients.

Identifiers

PMID30276052
PMCPMC6157929
OpenAlexW2807716775

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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.