ArticleStem cells (Dayton, Ohio)2012
Human T-lymphoid progenitors generated in a feeder-cell-free Delta-like-4 culture system promote T-cell reconstitution in NOD/SCID/γc(-/-) mice.
Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Thymic Epithelium Abnormalities in DiGeorge and Down Syndrome Patients Contribute to Dysregulation in T Cell Development.Frontiers in immunology · 2019Trial
- Advancing adoptive cellular immunotherapy via Notch-based ex vivo T cell development platforms.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Generation of thymus-reconstituting T cell progenitors from human pluripotent stem cells.Cell reports methods · 2026Article
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
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- Generation ofHeliyon · 2024Article
- Development of anMolecular therapy. Methods & clinical development · 2023Article
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- Multi-objective optimization reveals time- and dose-dependent inflammatory cytokine-mediated regulation of human stem cell derived T-cell development.NPJ Regenerative medicine · 2022Article
- T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation.Frontiers in immunology · 2022Review
- Thymus Reconstitution in Young and Aged Mice Is Facilitated byFrontiers in immunology · 2022Article
- Article
- DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system.Nature communications · 2021Article
- A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors.Cellular & molecular immunology · 2021Article
- Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans.Nature communications · 2021Article
- A gain-of-function RAC2 mutation is associated with bone-marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency.Haematologica · 2021Article
- The role of the thymus in allogeneic bone marrow transplantation and the recovery of the peripheral T-cell compartment.Seminars in immunopathology · 2021Review
- A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy.Nature communications · 2021Article
- Baboon Envelope Pseudotyped "Nanoblades" Carrying Cas9/gRNA Complexes Allow Efficient Genome Editing in Human T, B, and CD34Frontiers in genome editing · 2021Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Slow T-cell reconstitution is a major clinical concern after transplantation of cord blood (CB)-derived hematopoietic stem cells. Adoptive transfer of in vitro-generated T-cell progenitors has emerged as a promising strategy for promoting de novo thymopoiesis and thus accelerating T-cell reconstitution. Here, we describe the development of a new culture system based on the immobilized Notch ligand Delta-like-4 (DL-4). Culture of human CD34(+) CB cells in this new DL-4 system enabled the in vitro generation of large amounts of T-cell progenitor cells that (a) displayed the phenotypic and molecular signatures of early thymic progenitors and (b) had high T lymphopoietic potential. When transferred into NOD/SCID/γc(-/-) (NSG) mice, DL-4 primed T-cell progenitors migrated to the thymus and developed into functional, mature, polyclonal αβ T cells that subsequently left the thymus and accelerated T-cell reconstitution. T-cell reconstitution was even faster and more robust when ex vivo-manipulated and nonmanipulated CB samples were simultaneously injected into NSG mice (i.e., a situation reminiscent of the double CB transplant setting). This work provides further evidence of the ability of in vitro-generated human T-cell progenitors to accelerate T-cell reconstitution and also introduces a feeder-cell-free culture technique with the potential for rapid, safe transfer to a clinical setting.
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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.