Evidence map›Paper›PMID 34162938›Full record

ArticleScientific reports2021

Genetic engineering of porcine endothelial cell lines for evaluation of human-to-pig xenoreactive immune responses.

Ping Li, Julia R Walsh, Kevin Lopez, Abdulkadir Isidan, Wenjun Zhang, Angela M Chen, William C Goggins, Nancy G Higgins, Jianyun Liu, Randy R Brutkiewicz and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.1field-weighted citation impact, top 13% 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, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Cytotoxic Responses Mediated by NK Cells and Cytotoxic T Lymphocytes in Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Ping LiDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. pili@iupui.edu.ORCID 0000-0003-1055-9505
Julia R WalshDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-6637-7191
Kevin LopezDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-5807-3136
Abdulkadir IsidanDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-6655-1268
Wenjun ZhangDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-9801-0634
Angela M ChenDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-6716-2088
William C GogginsDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-9854-1574
Nancy G HigginsIndiana University Health, Indianapolis, IN, USA.ORCID 0000-0002-7575-7150
Jianyun LiuDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-6731-0375
Randy R BrutkiewiczDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-7396-480X
Lester J SmithRadiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0003-4950-7569
Hidetaka HaraXenotransplantation Program, Department of Surgery, University of Birmingham at Alabama, Birmingham, AL, USA.ORCID 0000-0002-4179-7365
David K C CooperXenotransplantation Program, Department of Surgery, University of Birmingham at Alabama, Birmingham, AL, USA.ORCID 0000-0002-8899-9431
Burcin EkserDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. bekser@iupui.edu.ORCID 0000-0003-0741-8007
Indiana University School of MedicineUniversity of Alabama at Birmingham · USIndiana University Health · USWeldon City Schools · US

Funding

Development of novel strategies to modulate human NK cell response in xenotransplantationR21AI164002 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI LI, PING · 2021 to 2022
$436k
NIAID NIH HHS R21 AI164002
6 · The paper itself

Abstract

Xenotransplantation (cross-species transplantation) using genetically-engineered pig organs offers a potential solution to address persistent organ shortage. Current evaluation of porcine genetic modifications is to monitor the nonhuman primate immune response and survival after pig organ xenotransplantation. This measure is an essential step before clinical xenotransplantation trials, but it is time-consuming, costly, and inefficient with many variables. We developed an efficient approach to quickly examine human-to-pig xeno-immune responses in vitro. A porcine endothelial cell was characterized and immortalized for genetic modification. Five genes including GGTA1, CMAH, β4galNT2, SLA-I α chain, and β2-microglobulin that are responsible for the production of major xenoantigens (αGal, Neu5Gc, Sda, and SLA-I) were sequentially disrupted in immortalized porcine endothelial cells using CRISPR/Cas9 technology. The elimination of αGal, Neu5Gc, Sda, and SLA-I dramatically reduced the antigenicity of the porcine cells, though the cells still retained their ability to provoke human natural killer cell activation. In summary, evaluation of human immune responses to genetically modified porcine cells in vitro provides an efficient method to identify ideal combinations of genetic modifications for improving pig-to-human compatibility, which should accelerate the application of xenotransplantation to humans.

Indexed as

AnimalsAnimals, Genetically ModifiedAntibodies, HeterophileAntigen-Antibody ReactionsAntigens, Heterophilebeta 2-MicroglobulinCell DegranulationCell Line, TransformedCRISPR-Cas SystemsCytokinesEndothelial CellsGalactosyltransferasesGene Knockout TechniquesGraft RejectionHistocompatibility Antigens Class IHumansalpha-1,3-galactosyltransferase 1, porcineAntibodies, HeterophileAntigens, Heterophilebeta-1,4-N-acetyl-galactosaminyl transferase 2beta 2-MicroglobulinCMPacetylneuraminate monooxygenaseCytokinesGalactosyltransferasesHistocompatibility Antigens Class IMixed Function OxygenasesN-Acetylgalactosaminyltransferasesswine leukocyte antigen

Identifiers

PMID34162938
PMCPMC8222275
OpenAlexW3175210674

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.