Evidence map›Paper›PMID 34407395›Full record

ArticleCell reports2021

Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection.

Audrey V Parent, Gaetano Faleo, Jessica Chavez, Michael Saxton, David I Berrios, Natanya R Kerper, Qizhi Tang, Matthias Hebrok

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
–field-weighted citation impact
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

60 citing papers in PubMed.

  1. Review
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  3. Article
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  6. Article
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  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Engineering hypoimmune stem cell-derived beta cells.Stem cell research & therapy · 2025
    Review
  14. Review
  15. Review
  16. A Cure for Type 1 Diabetes: Are We There Yet?Diabetes technology & therapeutics · 2025
    Review
  17. Review
  18. Cell Therapy for T1D Beyond BLA: Gearing Up Toward Clinical Practice.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025
    Review
  19. Review
  20. Review
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

8 authors.

Audrey V ParentDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: audrey.parent@ucsf.edu.
Gaetano FaleoDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Jessica ChavezDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Michael SaxtonDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
David I BerriosDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Natanya R KerperDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Qizhi TangDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Matthias HebrokDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: matthias.hebrok@ucsf.edu.

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
NIDDK NIH HHS P30 DK063720
6 · The paper itself

Abstract

Stem cell-based replacement therapies hold the promise to restore function of damaged or degenerated tissue such as the pancreatic islets in people with type 1 diabetes. Wide application of these therapies requires overcoming the fundamental roadblock of immune rejection. To address this issue, we use genetic engineering to create human pluripotent stem cells (hPSCs) in which the majority of the polymorphic human leukocyte antigens (HLAs), the main drivers of allogeneic rejection, are deleted. We retain the common HLA class I allele HLA-A2 and less polymorphic HLA-E/F/G to allow immune surveillance and inhibition of natural killer (NK) cells. We employ a combination of in vitro assays and humanized mouse models to demonstrate that these gene manipulations significantly reduce NK cell activity and T-cell-mediated alloimmune response against hPSC-derived islet cells. In summary, our approach produces hypoimmunogenic hPSCs that can be readily matched with recipients to avoid alloimmune rejection.

Indexed as

Gene DeletionAllelesAnimalsCell LineClone CellsGraft RejectionHLA AntigensHumansIslets of LangerhansKiller Cells, NaturalLymphocyte ActivationMaleMiceMice, Inbred NODPluripotent Stem CellsT-LymphocytesHLA Antigensbeta cell replacement therapycell therapydiabeteshuman leukocyte antigensimmune evasionimmune rejectionpancreatic beta cellsregenerative medicinestem cells

Identifiers

PMID34407395
PMCPMC12416289

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.