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Efficient generation of thymic epithelium from induced pluripotent stem cells that prolongs allograft survival

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Title: Efficient generation of thymic epithelium from induced pluripotent stem cells that prolongs allograft survival
Authors: Otsuka, Ryo Browse this author
Wada, Haruka Browse this author →KAKEN DB
Tsuji, Hyuma Browse this author
Sasaki, Airi Browse this author
Murata, Tomoki Browse this author
Itoh, Mizuho Browse this author
Baghdadi, Muhammad Browse this author →KAKEN DB
Seino, Ken-Ichiro Browse this author →KAKEN DB
Issue Date: 14-Jan-2020
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 10
Issue: 1
Start Page: 224
Publisher DOI: 10.1038/s41598-019-57088-1
Abstract: 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.
Type: article
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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