| First Author | Wang M | Year | 2012 |
| Journal | Sci Transl Med | Volume | 4 |
| Issue | 133 | Pages | 133ra59 |
| PubMed ID | 22572882 | Mgi Jnum | J:186662 |
| Mgi Id | MGI:5432854 | Doi | 10.1126/scitranslmed.3003835 |
| Citation | Wang M, et al. (2012) Mixed chimerism and growth factors augment beta cell regeneration and reverse late-stage type 1 diabetes. Sci Transl Med 4(133):133ra59 |
| abstractText | Type 1 diabetes (T1D) results from an autoimmune destruction of insulin-producing beta cells. Currently, islet transplantation is the only curative therapy for late-stage T1D, but the beneficial effect is limited in its duration, even under chronic immunosuppression, because of the chronic graft rejection mediated by both auto- and alloimmunity. Clinical islet transplantation is also restricted by a severe shortage of donor islets. Induction of mixed chimerism reverses autoimmunity, eliminates insulitis, and reverses new-onset but not late-stage disease in the nonobese diabetic (NOD) mouse model of T1D. Administration of gastrin and epidermal growth factor (EGF) also reverses new-onset but not late-stage T1D in this animal model. Here, we showed that combination therapy of induced mixed chimerism under a radiation-free nontoxic anti-CD3/CD8 conditioning regimen and administration of gastrin/EGF augments both beta cell neogenesis and replication, resulting in reversal of late-stage T1D in NOD mice. If successfully translated into humans, this combination therapy could replace islet transplantation as a long-term curative therapy for T1D. |
