Reversal of autoimmunity by mixed chimerism enables reactivation of β cells and transdifferentiation of α cells in diabetic NOD mice.

ABSTRACT: Type 1 diabetes (T1D) results from the autoimmune destruction of β cells, so cure of firmly established T1D requires both reversal of autoimmunity and restoration of β cells. It is known that β cell regeneration in nonautoimmune diabetic mice can come from differentiation of progenitors and/or transdifferentiation of α cells. However, the source of β cell regeneration in autoimmune nonobese diabetic (NOD) mice remains unclear. Here, we show that, after reversal of autoimmunity by induction of haploidentical mixed chimerism, administration of gastrin plus epidermal growth factor augments β cell regeneration and normalizes blood glucose in the firmly established diabetic NOD mice. Using transgenic NOD mice with inducible lineage-tracing markers for insulin-producing β cells, Sox9⁺

SUBMITTER: Tang S 

PROVIDER: S-EPMC7733788 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature