| First Author | Tang S | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 49 | Pages | 31219-31230 |
| PubMed ID | 33229527 | Mgi Jnum | J:299211 |
| Mgi Id | MGI:6479937 | Doi | 10.1073/pnas.2012389117 |
| Citation | Tang S, et al. (2020) Reversal of autoimmunity by mixed chimerism enables reactivation of beta cells and transdifferentiation of alpha cells in diabetic NOD mice. Proc Natl Acad Sci U S A 117(49):31219-31230 |
| abstractText | Type 1 diabetes (T1D) results from the autoimmune destruction of beta cells, so cure of firmly established T1D requires both reversal of autoimmunity and restoration of beta cells. It is known that beta cell regeneration in nonautoimmune diabetic mice can come from differentiation of progenitors and/or transdifferentiation of alpha cells. However, the source of beta 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 beta 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 beta cells, Sox9(+) ductal progenitors, Nestin(+) mesenchymal stem cells, and glucagon-producing alpha cells, we have found that both reactivation of dysfunctional low-level insulin expression (insulin(lo)) beta cells and neogenesis contribute to the regeneration, with the latter predominantly coming from transdifferentiation of alpha cells. These results indicate that, after reversal of autoimmunity, reactivation of beta cells and transdifferentiation of alpha cells can provide sufficient new functional beta cells to reach euglycemia in firmly established T1D. |
