ArticleJournal of cellular and molecular medicine2019
Silencing of HLA class I on primary human hepatocytes as a novel strategy for reduction in alloreactivity.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
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- Immunological Response against Breast Lineage Cells Transfected with Human Papillomavirus (HPV).Viruses · 2024Article
- Human Hepatocyte Transplantation: Three Decades of Clinical Experience and Future Perspective.Stem cells translational medicine · 2024Review
- Machine Perfusion and Bioengineering Strategies in Transplantation-Beyond the Emerging Concepts.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Recent Advances in Models of Immune-Mediated Drug-Induced Liver Injury.Frontiers in toxicology · 2021Review
- Fit-For-All iPSC-Derived Cell Therapies and Their Evaluation in Humanized Mice With NK Cell Immunity.Frontiers in immunology · 2021Review
- Genetic Modification of Limbal Stem Cells to Decrease Allogeneic Immune Responses.Frontiers in immunology · 2021Article
- Generating low immunogenic pig pancreatic islet cell clusters for xenotransplantation.Journal of cellular and molecular medicine · 2020Article
- Transplant Tolerance Induction: Insights From the Liver.Frontiers in immunology · 2020Review
- Silencing of HLA class I on primary human hepatocytes as a novel strategy for reduction in alloreactivity.Journal of cellular and molecular medicine · 2019Article
- Mechanisms of Immune Tolerance in Liver Transplantation-Crosstalk Between Alloreactive T Cells and Liver Cells With Therapeutic Prospects.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In contrast to the whole liver, primary hepatocytes are highly immunogenic. Thus, alternative strategies of immunomodulation after hepatocyte transplantation are of special interest. Silencing of HLA class I expression is expected to reduce the strength of allogeneic immune responses and to improve graft survival. In this study, primary human hepatocytes (PHH) were isolated using a two-step-collagenase perfusion-technique and co-cultured with allogeneic lymphocytes in terms of a mixed lymphocyte hepatocyte culture. Expression of HLA class I on PHH was silenced using lentiviral vectors encoding for β2-microglobulin-specific short hairpin RNA (shβ2m) or non-specific shRNA (shNS) as control. The delivery of shβ2m into PHH caused a decrease by up to 96% in β2m transcript levels and a down-regulation of HLA class I cell surface expression on PHH by up to 57%. Proliferative T cell alloresponses against HLA-silenced PHH were significantly lower than those observed form fully HLA-expressing PHH. In addition, significantly lower secretion of pro-inflammatory cytokines was observed. Levels of albumin, urea and aspartate-aminotransferase did not differ in supernatants of cultured PHH. In conclusion, silencing HLA class I expression on PHH might represent a promising approach for immunomodulation in the transplant setting without compromising metabolic function of silenced hepatocytes.
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Registered trials
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