Transplantation of MHC-mismatched mouse embryonic stem cell-derived thymic epithelial progenitors and MHC-matched bone marrow prevents autoimmune diabetes

Stem Cell Research & Therapy
Min SuLaijun Lai

Abstract

Type 1 diabetes (T1D) is an autoimmune disease resulting from the destruction of insulin-secreting islet β cells by autoreactive T cells. Non-obese diabetic (NOD) mice are the widely used animal model for human T1D. Autoimmunity in NOD mice is associated with particular major histocompatibility complex (MHC) loci and impaired islet autoantigen expression and/or presentation in the thymus, which results in defects in both central and peripheral tolerance. It has been reported that induction of mixed chimerism with MHC-mismatched, but not MHC-matched donor bone marrow (BM) transplants prevents the development T1D in NOD mice. We have reported that mouse embryonic stem cells (mESCs) can be selectively induced in vitro to generate thymic epithelial progenitors (TEPs) that further develop into thymic epithelial cells (TECs) in vivo to support T cell development. To determine whether transplantation of MHC-mismatched mESC-TEPs could prevent the development of insulitis and T1D, NOD mice were conditioned and injected with MHC-mismatched B6 mESC-TEPs and MHC-matched BM from H-2g7 B6 mice. The mice were monitored for T1D development. The pancreas, spleen, BM, and thymus were then harvested from the mice for evaluation of T1D, insulitis,...Continue Reading

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Citations

May 4, 2021·EMBO Molecular Medicine·Yujun LinLaijun Lai
Jul 27, 2021·Advanced Science·Himal Sharma, Lorenzo Moroni
Jul 2, 2021·Advanced Healthcare Materials·Catarina S SilvaNuno M Neves

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Methods Mentioned

BETA
transgenic
scintillation spectroscopy
flow cytometry
FACS

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