Evidence map›Paper›PMID 34695489›Full record

ArticleThe Journal of allergy and clinical immunology2022

Human stem cell-derived thymic epithelial cells enhance human T-cell development in a xenogeneic thymus.

Rafael Gras-Peña, Nichole M Danzl, Mohsen Khosravi-Maharlooei, Sean R Campbell, Amanda E Ruiz, Christopher A Parks, William Meng Suen Savage, Markus A Holzl, Debanjana Chatterjee, Megan Sykes

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2022. 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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Thymus Ontogeny and Development.Advances in experimental medicine and biology · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Inborn errors of immunity associated with defects of thymic development.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022
    Review
  15. Review
  16. Frontiers in endocrinology · 2022
    Review
  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Rafael Gras-PeñaColumbia Center for Human Development, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY; Columbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY. Electronic address: rg2837@cumc.columbia.edu.
Nichole M DanzlColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Mohsen Khosravi-MaharlooeiColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Sean R CampbellColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Amanda E RuizColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Christopher A ParksColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
William Meng Suen SavageColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Markus A HolzlColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Debanjana ChatterjeeColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY.
Megan SykesColumbia Center for Translational Immunology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY; Department of Surgery and Department of Microbiology and Immunology, Columbia University, New York, NY. Electronic address: megan.sykes@columbia.edu.
Columbia University · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
XENOGRAFT TOLERANCE THROUGH MIXED CHIMERISMP01AI045897 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Megan Sykes · 2000 to 2026
$71.9M
Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systemsU01DK123559 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDERSON, MARK S, PARENT, AUDREY · 2019 to 2023
$4.3M
Mice with autologous human T1D-derived immune systems and iPSC-derived beta cellsUC4DK104207 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SYKES, MEGAN · 2014 to 2014
$3.8M
Multidisciplinary Training in Molecular and Translational Rheumatology ResearchT32AR076953 · NIAMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BATHON, JOAN MARIE, WINCHESTER, ROBERT J · 2021 to 2025
$742k
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
Cell intrinsic immunopathology of Type I diabetes in humanized miceF32DK095539 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DANZL, NICHOLE MARIE · 2012 to 2014
$173k
NCI NIH HHS P30 CA013696NCRR NIH HHS S10 RR027050NIAID NIH HHS P01 AI045897NIAMS NIH HHS T32 AR076953NIDDK NIH HHS F32 DK095539NIDDK NIH HHS U01 DK123559NIDDK NIH HHS UC4 DK104207
6 · The paper itself

Abstract

backgroundGeneration of thymic tissue from pluripotent stem cells would provide therapies for acquired and congenital thymic insufficiency states.

objectivesThis study aimed to generate human thymic epithelial progenitors from human embryonic stem cells (hES-TEPs) and to assess their thymopoietic function in vivo.

methodsThis study differentiated hES-TEPs by mimicking developmental queues with FGF8, retinoic acid, SHH, Noggin, and BMP4. Their function was assessed in reaggregate cellular grafts under the kidney capsule and in hybrid thymi by incorporating them into swine thymus (SwTHY) grafts implanted under the kidney capsules of immunodeficient mice that received human hematopoietic stem and progenitor cells (hHSPCs) intravenously.

resultsCultured hES-TEPs expressed FOXN1 and formed colonies expressing EPCAM and both cortical and medullary thymic epithelial cell markers. In thymectomized immunodeficient mice receiving hHSPCs, hES-TEPs mixed with human thymic mesenchymal cells supported human T-cell development. Hypothesizing that support from non-epithelial thymic cells might allow long-term function of hES-TEPs, the investigators injected them into SwTHY tissue, which supports human thymopoiesis in NOD severe combined immunodeficiency IL2Rγ

conclusionsThis study has developed and demonstrated in vivo thymopoietic function of hES-TEPs generated with a novel differentiation protocol. The SwTHY hybrid thymus model demonstrates beneficial effects on human thymocyte development of hES-TEPs maturing in the context of a supportive thymic structure.

Indexed as

Epithelial CellsThymocytesAnimalsCell DifferentiationEpitheliumHumansMiceMice, Inbred NODThymus GlandEmbryonic stem cell differentiationTECthird pharyngeal pouchthymusxenotransplantation

Identifiers

PMID34695489
PMCPMC9023620
OpenAlexW3207674729

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.