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Efficient generation of thymic epithelium from induced pluripotent stem cells that prolongs allograft survival
The thymus plays a significant role in establishing immunological self-tolerance. Previous studies have revealed that host immune reaction to allogeneic transplants could be regulated by thymus transplantation. However, physiological thymus involution hinders the clinical application of these insigh...
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Published in: | Scientific reports 2020-01, Vol.10 (1), p.224-224, Article 224 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The thymus plays a significant role in establishing immunological self-tolerance. Previous studies have revealed that host immune reaction to allogeneic transplants could be regulated by thymus transplantation. However, physiological thymus involution hinders the clinical application of these insights. Here, we report an efficient generation of thymic epithelial-like tissue derived from induced pluripotent stem cells (iPSCs) and its potential to regulate immune reaction in allogeneic transplantation. We established an iPSC line which constitutively expresses mouse
Foxn1
gene and examined the effect of its expression during
in vitro
differentiation of thymic epithelial cells (TECs). We found that
Foxn1
expression enhances the differentiation induction of cells expressing TEC-related cell surface molecules along with upregulation of endogenous
Foxn1
. iPSC-derived TECs (iPSC-TECs) generated T cells in nude recipient mice after renal subcapsular transplantation. Moreover, iPSC-TEC transplantation to immuno-competent recipients significantly prolonged the survival of allogeneic skin. Our study provides a novel concept for allogeneic transplantation in the setting of regenerative medicine. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-019-57088-1 |