ArticleStem cells translational medicine2019
Gene Modification and Three-Dimensional Scaffolds as Novel Tools to Allow the Use of Postnatal Thymic Epithelial Cells for Thymus Regeneration Approaches.
Article in Stem cells translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Network-orchestrated regulation of thymic dysfunction and restoration.Frontiers in immunology · 2026Review
- Unlocking Transplant Tolerance with Biomaterials.Advanced healthcare materials · 2025Review
- Rediscovering the human thymus through cutting-edge technologies.The Journal of experimental medicine · 2024Review
- Swim bladder-derived biomaterials: structures, compositions, properties, modifications, and biomedical applications.Journal of nanobiotechnology · 2024Review
- Comparison of Elicitation Approaches in Early Stage HTA Applied on Artificial Thymus for Patients with DiGeorge Syndrome.Healthcare (Basel, Switzerland) · 2023Article
- The potential role of the thymus in immunotherapies for acute myeloid leukemia.Frontiers in immunology · 2023Review
- Congenital Athymia: Unmet Needs and Practical Guidance.Therapeutics and clinical risk management · 2023Review
- 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 · 2022Review
- Progress on methods of T lymphocyte developmentZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Thymic Extracellular Matrix in the Thymopoiesis: Just a Supporting?Biotech (Basel (Switzerland)) · 2022Article
- Editing T cell repertoire by thymic epithelial cell-directed gene transfer abrogates risk of type 1 diabetes development.Molecular therapy. Methods & clinical development · 2022Article
- Differentiation of Pluripotent Stem Cells Into Thymic Epithelial Cells and Generation of Thymic Organoids: Applications for Therapeutic Strategies Against APECED.Frontiers in immunology · 2022Review
- Recent Advancements in Regenerative Approaches for Thymus Rejuvenation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Thymus Extracellular Matrix-Derived Scaffolds Support Graft-Resident Thymopoiesis and Long-Term In Vitro Culture of Adult Thymic Epithelial Cells.Advanced functional materials · 2021Article
- T cell regeneration after immunological injury.Nature reviews. Immunology · 2021Review
- Nanotechnological approach and bio-inspired materials to face degenerative diseases in aging.Aging clinical and experimental research · 2021Review
- The contribution of thymic tolerance to central nervous system autoimmunity.Seminars in immunopathology · 2021Review
- The role of the thymus in allogeneic bone marrow transplantation and the recovery of the peripheral T-cell compartment.Seminars in immunopathology · 2021Review
- Immune Reconstitution After Allogeneic Haematopoietic Cell Transplantation: From Observational Studies to Targeted Interventions.Frontiers in pediatrics · 2021Review
- Research Progress, Challenges, and Breakthroughs of Organoids as Disease Models.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective functionality of thymic epithelial cells (TECs), due to genetic mutations or injuring causes, results in altered T-cell development, leading to immunodeficiency or autoimmunity. These defects cannot be corrected by hematopoietic stem cell transplantation (HSCT), and thymus transplantation has not yet been demonstrated to be fully curative. Here, we provide proof of principle of a novel approach toward thymic regeneration, involving the generation of thymic organoids obtained by seeding gene-modified postnatal murine TECs into three-dimensional (3D) collagen type I scaffolds mimicking the thymic ultrastructure. To this end, freshly isolated TECs were transduced with a lentiviral vector system, allowing for doxycycline-induced Oct4 expression. Transient Oct4 expression promoted TECs expansion without drastically changing the cell lineage identity of adult TECs, which retain the expression of important molecules for thymus functionality such as Foxn1, Dll4, Dll1, and AIRE. Oct4-expressing TECs (iOCT4 TEC) were able to grow into 3D collagen type I scaffolds both in vitro and in vivo, demonstrating that the collagen structure reproduced a 3D environment similar to the thymic extracellular matrix, perfectly recognized by TECs. In vivo results showed that thymic organoids transplanted subcutaneously in athymic nude mice were vascularized but failed to support thymopoiesis because of their limited in vivo persistence. These findings provide evidence that gene modification, in combination with the usage of 3D biomimetic scaffolds, may represent a novel approach allowing the use of postnatal TECs for thymic regeneration. Stem Cells Translational Medicine 2019;8:1107-1122.
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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.