Evidence map›Paper›PMID 26218149›Full record

ArticleTissue engineering. Part A2015

HLA Class I Depleted hESC as a Source of Hypoimmunogenic Cells for Tissue Engineering Applications.

Zaruhi Karabekian, Hao Ding, Gulnaz Stybayeva, Irina Ivanova, Narine Muselimyan, Amranul Haque, Ian Toma, Nikki G Posnack, Alexander Revzin, David Leitenberg and 2 more

Abstract read
In one paragraph

Article in Tissue engineering. Part A, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Review
  3. Frontiers in immunology · 2025
    Review
  4. Review
  5. Review
  6. Maintenance of Hypoimmunogenic FeaturesFrontiers in bioengineering and biotechnology · 2022
    Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. 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

12 authors at 1 institution in 1 country.

Zaruhi Karabekian1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
Hao Ding1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
Gulnaz Stybayeva3 Department of Biomedical Engineering, University of California Davis , Davis, California.
Irina Ivanova1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
Narine Muselimyan1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
Amranul Haque3 Department of Biomedical Engineering, University of California Davis , Davis, California.
Ian Toma1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
Nikki G Posnack1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
Alexander Revzin3 Department of Biomedical Engineering, University of California Davis , Davis, California.
David Leitenberg1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
Michael A Laflamme4 Institute for Stem Cell and Regenerative Medicine, Center for Cardiovascular Biology, University of Washington , Seattle, Washington.
Narine Sarvazyan1 Pharmacology and Physiology Department, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia.
University of California, Davis · US

Funding

Cardiomyocyte-derived Venous Assist Device: Aiding peripheral blood flowR21HL122882 · NHLBI · GEORGE WASHINGTON UNIVERSITY · PI SARVAZYAN, NARINE · 2015 to 2016
$432k
NHLBI NIH HHS R21 HL122882
6 · The paper itself

Abstract

backgroundRapidly improving protocols for the derivation of autologous cells from stem cell sources is a welcome development. However, there are many circumstances when off-the-shelf universally immunocompatible cells may be needed. Embryonic stem cells (ESCs) provide a unique opportunity to modify the original source of differentiated cells to minimize their rejection by nonautologous hosts. HYPOTHESIS: Immune rejection of nonautologous human embryonic stem cell (hESC) derivatives can be reduced by downregulating human leukocyte antigen (HLA) class I molecules, without affecting the ability of these cells to differentiate into specific lineages. METHODS AND

resultsBeta-2-microglobulin (B2M) expression was decreased by lentiviral transduction using human anti-HLA class I light-chain B2M short hairpin RNA. mRNA levels of B2M were decreased by 90% in a RUES2-modified hESC line, as determined by quantitative real time-polymerase chain reaction analysis. The transduced cells were selected under puromycin pressure and maintained in an undifferentiated state. The latter was confirmed by Oct4 and Nanog expression, and by the formation of characteristic round-shaped colonies. B2M downregulation led to diminished HLA-I expression on the cell surface, as determined by flow cytometry. When used as target cells in a mixed lymphocyte reaction assay, transduced hESCs and their differentiated derivatives did not stimulate allogeneic T-cell proliferation. Using a cardiac differentiation protocol, transduced hESCs formed a confluent layer of cardiac myocytes and maintained a low level of B2M expression. Transduced hESCs were also successfully differentiated into a hepatic lineage, validating their capacity to differentiate into multiple lineages.

conclusionsHLA-I depletion does not preclude hESC differentiation into cardiac or hepatic lineages. This methodology can be used to engineer tissue from nonautologous hESC sources with improved immunocompatibility.

Indexed as

Cell DifferentiationCell LineCell ProliferationEmbryonic Stem CellsFlow CytometryHistocompatibility Antigens Class IHumansImmunohistochemistryPluripotent Stem CellsTissue EngineeringHistocompatibility Antigens Class I

Identifiers

PMID26218149
PMCPMC4605353
OpenAlexW1537863311

What OpenQuestion holds

Textmetadata
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.