ArticleCytotherapy2014
Third-party umbilical cord blood-derived regulatory T cells prevent xenogenic graft-versus-host disease.
Article in Cytotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- Use of regulatory cells for achieving functional tolerance of pig heart xenotransplants in humans: a literature review.Frontiers in immunology · 2025Review
- Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice.Biomarker research · 2024Review
- CXCR4-enriched T regulatory cells preferentially home to bone marrow and resolve inflammation.iScience · 2024Article
- Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes.Frontiers in transplantation · 2024Article
- Regulatory T cells in lung disease and transplantation.Bioscience reports · 2023Review
- Article
- Manufacturing regulatory T cells for adoptive cell therapy in immune diseases: A critical appraisal.Clinical immunology (Orlando, Fla.) · 2023Review
- Allogeneic cord blood regulatory T cells can resolve lung inflammation.Cytotherapy · 2023Article
- Allogeneic cord blood regulatory T cells decrease dsDNA antibody and improve albuminuria in systemic lupus erythematosus.Frontiers in immunology · 2023Article
- Barriers to Treg therapy in Europe: From production to regulation.Frontiers in medicine · 2023Review
- Insights into mechanisms of graft-versus-host disease through humanised mouse models.Bioscience reports · 2022Review
- Combined treatment of graft versus host disease using donor regulatory T cells and ruxolitinib.Scientific reports · 2022Article
- Haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood in hematologic malignancy patients: A report of 80 cases.Frontiers in immunology · 2022Article
- Mesenchymal stromal cell mitochondrial transfer to human induced T-regulatory cells mediates FOXP3 stability.Scientific reports · 2021Article
- Regulatory T Cells in GVHD Therapy.Frontiers in immunology · 2021Review
- TNature reviews. Immunology · 2020Review
- Cryopreservation timing is a critical process parameter in a thymic regulatory T-cell therapy manufacturing protocol.Cytotherapy · 2019Article
- Methods to manufacture regulatory T cells for cell therapy.Clinical and experimental immunology · 2019Review
- Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients.JCI insight · 2019Article
- GM-CSF Promotes the Expansion and Differentiation of Cord Blood Myeloid-Derived Suppressor Cells, Which Attenuate Xenogeneic Graft-vs.-Host Disease.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND
aimsNaturally occurring regulatory T cells (Treg) are emerging as a promising approach for prevention of graft-versus-host disease (GvHD), which remains an obstacle to the successful outcome of allogeneic hematopoietic stem cell transplantation. However, Treg only constitute 1-5% of total nucleated cells in cord blood (CB) (<3 × 10⁶ cells), and therefore novel methods of Treg expansion to generate clinically relevant numbers are needed.
methodsSeveral methodologies are currently being used for ex vivo Treg expansion. We report a new approach to expand Treg from CB and demonstrate their efficacy in vitro by blunting allogeneic mixed lymphocyte reactions and in vivo by preventing GvHD through the use of a xenogenic GvHD mouse model.
resultsWith the use of magnetic cell sorting, naturally occurring Treg were isolated from CB by the positive selection of CD25⁺ cells. These were expanded to clinically relevant numbers by use of CD3/28 co-expressing Dynabeads and interleukin (IL)-2. Ex vivo-expanded Treg were CD4⁺25⁺ FOXP3⁺127(lo) and expressed a polyclonal T-cell receptor, Vβ repertoire. When compared with conventional T-lymphocytes (CD4⁺25⁻ cells), Treg consistently showed demethylation of the FOXP3 TSDR promoter region and suppression of allogeneic proliferation responses in vitro.
conclusionsIn our NOD-SCID IL-2Rγ(null) xenogeneic model of GvHD, prophylactic injection of third-party, CB-derived, ex vivo-expanded Treg led to the prevention of GvHD that translated into improved GvHD score, decreased circulating inflammatory cytokines and significantly superior overall survival. This model of xenogenic GvHD can be used to study the mechanism of action of CB Treg as well as other therapeutic interventions.
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Registered trials
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.