Immunogenicity of human embryonic stem cell-derived beta cells
| العنوان: | Immunogenicity of human embryonic stem cell-derived beta cells |
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| المؤلفون: | Cornelis R. van der Torren, Bart O. Roep, Arnaud Zaldumbide, Mark Peakman, Gaby Duinkerken, Laura Martinson, Eugene P. Brandon, Geert Stange, Simone H. Brand-Schaaf, Daniel Pipeleers, Evert Kroon |
| المساهمون: | Medicine and Pharmacy academic/administration, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, Vriendenkring VUB |
| المصدر: | Diabetologia Diabetologia, 60(1), 126-133 Europe PubMed Central van der Torren, C R, Zaldumbide, A, Duinkerken, G, Brand-Schaaf, S H, Peakman, M, Stangé, G, Martinson, L, Kroon, E, Brandon, E P, Pipeleers, D & Roep, B O 2017, ' Immunogenicity of human embryonic stem cell-derived beta cells ', Diabetologia, vol. 60, no. 1, pp. 126–133 . https://doi.org/10.1007/s00125-016-4125-yTest |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Embryonic stem cells, Endocrinology, Diabetes and Metabolism, Human Embryonic Stem Cells, 030209 endocrinology & metabolism, Autoimmunity, Adaptive Immunity, Biology, Article, Allograft rejection, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Immune system, Insulin-Secreting Cells, HLA-A2 Antigen, Internal Medicine, Humans, Cells, Cultured, reproductive and urinary physiology, Stem cell transplantation for articular cartilage repair, geography, Transplantation, geography.geographical_feature_category, Stem Cells, Immunogenicity, Beta cells, Allografts, equipment and supplies, Islet, Embryonic stem cell, Immunity, Innate, Immunity, Humoral, 3. Good health, Cell biology, 030104 developmental biology, embryonic structures, Immunology, biological phenomena, cell phenomena, and immunity, Stem cell, Adult stem cell |
| الوصف: | Aims/hypothesis To overcome the donor shortage in the treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source of beta cells. hESCs may have immune privileged properties and it is important to determine whether these properties are preserved in hESC-derived cells. Methods We comprehensively investigated interactions of both innate and adaptive auto- and allo-immunity with hESC-derived pancreatic progenitor cells and hESC-derived endocrine cells, retrieved after in-vivo differentiation in capsules in the subcutis of mice. Results We found that hESC-derived pancreatic endodermal cells expressed relatively low levels of HLA endorsing protection from specific immune responses. HLA was upregulated when exposed to IFNγ, making these endocrine progenitor cells vulnerable to cytotoxic T cells and alloreactive antibodies. In vivo-differentiated endocrine cells were protected from complement, but expressed more HLA and were targets for alloreactive antibody-dependent cellular cytotoxicity and alloreactive cytotoxic T cells. After HLA compatibility was provided by transduction with HLA-A2, preproinsulin-specific T cells killed insulin-producing cells. Conclusions/interpretation hESC-derived pancreatic progenitors are hypoimmunogenic, while in vivo-differentiated endocrine cells represent mature targets for adaptive immune responses. Our data support the need for immune intervention in transplantation of hESC-derived pancreatic progenitors. Cell-impermeable macro-encapsulation may suffice. Electronic supplementary material The online version of this article (doi:10.1007/s00125-016-4125-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
| وصف الملف: | application/pdf |
| تدمد: | 0012-186X |
| DOI: | 10.1007/s00125-016-4125-y |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3e199117bcaa8f1323d2599c9034990Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e3e199117bcaa8f1323d2599c9034990 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0012186X |
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| DOI: | 10.1007/s00125-016-4125-y |