ArticleJCI insight2019
Progenitor-derived human endothelial cells evade alloimmunity by CRISPR/Cas9-mediated complete ablation of MHC expression.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
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Who cites it
22 citing papers in PubMed.
- Endothelial MHC expression is required to initiate T cell-mediated rejection of 3D-printed skin grafts.JCI insight · 2026Article
- An assessment of the functional state of endothelial colony forming cells from patients with diabetes mellitus and chronic limb threatening ischemia.Stem cells translational medicine · 2025Article
- Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells.Nature communications · 2025Article
- Vaxtherapy, a Multiphase Therapeutic Protocol Approach for Longvax, the COVID-19 Vaccine-Induced Disease: Spike Persistence as the Core Culprit and Its Downstream Effects.Diseases (Basel, Switzerland) · 2025Article
- The Interface of Gene Editing with Regenerative Medicine.Engineering (Beijing, China) · 2025Article
- Vascular endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering.Acta biomaterialia · 2025Article
- Cell manufacturing for cell-based tissue engineering: a focus on vascularized, skeletal muscle regeneration.Frontiers in chemical engineering · 2025Article
- IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Anti-inflammatory Prowess of endothelial progenitor cells in the realm of biology and medicine.NPJ Regenerative medicine · 2024Review
- mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.Circulation research · 2024Article
- The Transplant Bellwether: Endothelial Cells in Antibody-Mediated Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Hypoimmunogenic Human Pluripotent Stem Cells as a Powerful Tool for Liver Regenerative Medicine.International journal of molecular sciences · 2023Article
- 3D bioprinting of an implantable xeno-free vascularized human skin graft.Bioengineering & translational medicine · 2023Article
- Nucleic Acid Delivery to the Vascular Endothelium.Molecular pharmaceutics · 2022Review
- State of the field: cellular and exosomal therapeutic approaches in vascular regeneration.American journal of physiology. Heart and circulatory physiology · 2022Review
- Membrane attack complexes, endothelial cell activation, and direct allorecognition.Frontiers in immunology · 2022Review
- Single-Cell RNA Sequencing Identifies Intra-Graft Population Heterogeneity in Acute Heart Allograft Rejection in Mouse.Frontiers in immunology · 2022Article
- Immune Editing: Overcoming Immune Barriers in Stem Cell Transplantation.Current stem cell reports · 2022Review
- A therapeutic vascular conduit to support in vivo cell-secreted therapy.NPJ Regenerative medicine · 2021Article
- Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Tissue engineering may address organ shortages currently limiting clinical transplantation. Off-the-shelf engineered vascularized organs will likely use allogeneic endothelial cells (ECs) to construct microvessels required for graft perfusion. Vasculogenic ECs can be differentiated from committed progenitors (human endothelial colony-forming cells or HECFCs) without risk of mutation or teratoma formation associated with reprogrammed stem cells. Like other ECs, these cells can express both class I and class II major histocompatibility complex (MHC) molecules, bind donor-specific antibody (DSA), activate alloreactive T effector memory cells, and initiate rejection in the absence of donor leukocytes. CRISPR/Cas9-mediated dual ablation of β2-microglobulin and class II transactivator (CIITA) in HECFC-derived ECs eliminates both class I and II MHC expression while retaining EC functions and vasculogenic potential. Importantly, dually ablated ECs no longer bind human DSA or activate allogeneic CD4+ effector memory T cells and are resistant to killing by CD8+ alloreactive cytotoxic T lymphocytes in vitro and in vivo. Despite absent class I MHC molecules, these ECs do not activate or elicit cytotoxic activity from allogeneic natural killer cells. These data suggest that HECFC-derived ECs lacking MHC molecule expression can be utilized for engineering vascularized grafts that evade allorejection.
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