Evidence map›Paper›PMID 27813286›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2017

CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation-Resistant Tissues.

Jonathan M Brunger, Ananya Zutshi, Vincent P Willard, Charles A Gersbach, Farshid Guilak

Abstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.6field-weighted citation impact, top 4% 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

44 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
  2. Review
  3. Harnessing CRISPR potential for intervertebral disc regeneration strategies.Frontiers in bioengineering and biotechnology · 2025
    Review
  4. Article
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  9. A synthetic, closed-looped gene circuit for the autonomous regulation of RUNX2 activity during chondrogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  10. Article
  11. Review
  12. Article
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  14. Advanced Gene Therapy Strategies for the Repair of ACL Injuries.International journal of molecular sciences · 2022
    Review
  15. Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.Journal of tissue engineering and regenerative medicine · 2022
    Review
  16. Review
  17. Article
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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

5 authors at 3 institutions in 1 country.

Jonathan M BrungerDuke University, Durham, North Carolina.ORCID 0000-0001-7468-7982
Ananya ZutshiDuke University, Durham, North Carolina.
Vincent P WillardCytex Therapeutics, Durham, North Carolina.
Charles A GersbachDuke University, Durham, North Carolina.
Farshid GuilakWashington University and Shriners Hospitals for Children, St. Louis, Missouri.
Duke University · USCytex Therapeutics (United States) · USShriners Hospitals for Children - St. Louis · US

Funding

Thermally-Triggered Intra-articular Drug Delivery for OAP01AR050245 · NIAMS · DUKE UNIVERSITY · PI KRAUS, VIRGINIA · 2003 to 2012
$11.5M
VISCOELASTIC PROPERTIES OF NORMAL AND OA CHONDRONSR01AG015768 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 1998 to 2022
$7.7M
OBESITY, BIOMECHANICS, AND INFLAMMATION IN OSTEOARTHRITISR01AG046927 · NIA · WASHINGTON UNIVERSITY · PI GUILAK, FARSHID · 2013 to 2023
$3.2M
Mechanical and Osmotic Signaling in ChondrocytesR01AR048182 · NIAMS · DUKE UNIVERSITY · PI GUILAK, FARSHID · 2003 to 2013
$3.0M
Engineering Morphogenetic Factors for Enhanced Genetic ReprogrammingDP2OD008586 · OD · DUKE UNIVERSITY · PI GERSBACH, CHARLES A. · 2011 to 2011
$2.4M
Intrinsic Repair of the Knee MeniscusR01AR048852 · NIAMS · DUKE UNIVERSITY · PI GUILAK, FARSHID · 2007 to 2011
$1.4M
Genome Editing of Stem Cells for Analysis of Osteoarthritis Causal VariantsR21AR065956 · NIAMS · DUKE UNIVERSITY · PI GERSBACH, CHARLES A., GUILAK, FARSHID · 2014 to 2015
$382k
Scaffold-Mediated Gene Delivery for Engineering of Osteochondral TissuesR21AR067467 · NIAMS · DUKE UNIVERSITY · PI GERSBACH, CHARLES A., GUILAK, FARSHID · 2015 to 2016
$366k
Spatially Controlled Gene Delivery of Morphogenetic Factors from Woven ScaffoldsR03AR061042 · NIAMS · DUKE UNIVERSITY · PI GERSBACH, CHARLES A. · 2011 to 2013
$224k
NIAMS NIH HHS P01 AR050245NIAMS NIH HHS R01 AR048182NIAMS NIH HHS R01 AR048852NIAMS NIH HHS R03 AR061042NIAMS NIH HHS R21 AR065956NIAMS NIH HHS R21 AR067467NIA NIH HHS R01 AG015768NIA NIH HHS R01 AG046927NIH HHS DP2 OD008586
6 · The paper itself

Abstract

objectiveProinflammatory cytokines such as interleukin-1 (IL-1) are found in elevated levels in diseased or injured tissues and promote rapid tissue degradation while preventing stem cell differentiation. This study was undertaken to engineer inflammation-resistant murine induced pluripotent stem cells (iPSCs) through deletion of the IL-1 signaling pathway and to demonstrate the utility of these cells for engineering replacements for diseased or damaged tissues.

methodsTargeted deletion of the IL-1 receptor type I (IL-1RI) gene in murine iPSCs was achieved using the RNA-guided, site-specific clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome engineering system. Clonal cell populations with homozygous and heterozygous deletions were isolated, and loss of receptor expression and cytokine signaling was confirmed by flow cytometry and transcriptional reporter assays, respectively. Cartilage was engineered from edited iPSCs and tested for its ability to resist IL-1-mediated degradation in gene expression, histologic, and biomechanical assays after a 3-day treatment with 1 ng/ml of IL-1α.

resultsThree of 41 clones isolated possessed the IL-1RI

conclusionThis work demonstrates proof-of-concept of the ability to engineer custom-designed stem cells that are immune to proinflammatory cytokines (i.e., IL-1) as a potential cell source for cartilage tissue engineering.

Indexed as

ChondrogenesisCRISPR-Cas SystemsAnimalsCartilageChondrocytesFlow CytometryGene DeletionGene EditingGene ExpressionGene Expression RegulationInduced Pluripotent Stem CellsInflammationInterleukin-1MiceNF-kappa BReceptors, Interleukin-1Interleukin-1NF-kappa BReceptors, Interleukin-1

Identifiers

PMID27813286
PMCPMC5406241
OpenAlexW2552119924

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.