ArticleStem cells (Dayton, Ohio)2014
Generation of functional, antigen-specific CD8+ human T cells from cord blood stem cells using exogenous Notch and tetramer-TCR signaling.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Prognostic value of CD8Frontiers in immunology · 2024Article
- Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells.Immunological reviews · 2023Review
- Article
- Applications of molecular engineering in T-cell-based immunotherapies.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2019Review
- Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers.Theranostics · 2019Article
- Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1.Nature methods · 2017Article
- Engineering cord blood to improve engraftment after cord blood transplant.Stem cell investigation · 2017Review
- T Cell Genesis: In Vitro Veritas Est?Trends in immunology · 2016Review
- Engineering approaches for regeneration of T lymphopoiesis.Biomaterials research · 2016Review
- In Vitro T-Cell Generation From Adult, Embryonic, and Induced Pluripotent Stem Cells: Many Roads to One Destination.Stem cells (Dayton, Ohio) · 2015Review
- Umbilical cord blood-derived CD11c(+) dendritic cells could serve as an alternative allogeneic source of dendritic cells for cancer immunotherapy.Stem cell research & therapy · 2015Article
- Biomaterial Strategies for Immunomodulation.Annual review of biomedical engineering · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In vitro differentiation of mouse and human stem cells into early T cells has been successfully demonstrated using artificial Notch signaling systems. However, generation of mature, antigen-specific, functional T cells, directly from human stem cells has remained elusive, except when using stromal coculture of stem cells retrovirally transfected with antigen-specific T cell receptors (TCRs). Here we show that human umbilical cord blood (UCB)-derived CD34+CD38-/low hematopoietic stem cells can be successfully differentiated into functional, antigen-specific cytotoxic CD8+ T cells without direct stromal coculture or retroviral TCR transfection. Surface-immobilized Notch ligands (DLL1) and stromal cell conditioned medium successfully induced the development of CD1a+CD7+ and CD4+CD8+ early T cells. These cells, upon continued culture with cytomegalovirus (CMV) or influenza-A virus M1 (GIL) epitope-loaded human leukocyte antigen (HLA)-A*0201 tetramers, resulted in the generation of a polyclonal population of CMV-specific or GIL-specific CD8+ T cells, respectively. Upon further activation with antigen-loaded target cells, these antigen-specific, stem cell-derived T cells exhibited cytolytic functionality, specifically CD107a surface mobilization, interferon gamma (IFNg) production, and Granzyme B secretion. Such scalable, in vitro generation of functional, antigen-specific T cells from human stem cells could eventually provide a readily available cell source for adoptive transfer immunotherapies and also allow better understanding of human T cell development.
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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.