Open AccessTransplantation of Donor‐Origin Mouse Embryonic Stem Cell‐Derived Thymic Epithelial Progenitors Prevents the Development of Chronic Graft‐versus‐Host Disease in Mice
Author(s) -
Hu Rong,
Liu Yalan,
Su Min,
Song Yinhong,
Rood Debra,
Lai Laijun
Publication year - 2017
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.5966/sctm.2016-0012
Subject(s) - embryonic stem cell , progenitor cell , stem cell , immunology , transplantation , biology , graft versus host disease , hematopoietic stem cell transplantation , haematopoiesis , immune system , cancer research , medicine , microbiology and biotechnology , genetics , gene
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and nonmalignant diseases. However, chronic graft‐versus‐host disease (cGVHD) remains a significant cause of late morbidity and mortality after allogeneic HSCT. cGVHD often manifests as autoimmune syndrome. Thymic epithelial cells (TECs) play a critical role in supporting negative selection and regulatory T‐cell (Treg) generation. Studies have shown that damage in TECs is sufficient to induce cGVHD. We have previously reported that mouse embryonic stem cells (mESCs) can be selectively induced to generate thymic epithelial progenitors (TEPs) in vitro. When transplanted in vivo, mESC‐TEPs further develop into TECs that support T‐cell development. We show here that transplantation of donor‐origin mESC‐TEPs into cGVHD recipients induces immune tolerance to both donor and host antigens and prevents the development of cGVHD. This is associated with more TECs and Tregs. Our results suggest that embryonic stem cell‐derived TEPs may offer a new tool to control cGVHD. S tem C ells T ranslational M edicine 2017;6:121–130