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Sci Transl Med. 2012 May 9;4(133):133ra59. doi: 10.1126/scitranslmed.3003835.

Mixed chimerism and growth factors augment β cell regeneration and reverse late-stage type 1 diabetes.

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  • 1Departments of Diabetes Research and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.

Abstract

Type 1 diabetes (T1D) results from an autoimmune destruction of insulin-producing β 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 β 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.

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PMID:
22572882
[PubMed - indexed for MEDLINE]
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