BioRxiv. 2022 Sep 17
Quan Zhou, Hongfei Li, Dario Gerace, Igor Nikolskly, Xi Wang, Jennifer Kenty-Ryu, Jingping Zhang, Matthew Hinderhofer, Elaine Robinson and Douglas A. Melton
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AAV vector packaging ssAAV plasmids encoding Firefly luciferase (Luc2) (control) and Luc2-IL2N88D-TGFβ (experimental) (Fig. 6A) were packaged in AAV8-Y447F+Y773F(39) (PackGene) and injected i.p. into 4-week-old female NOD mice (n=10/group) (Jackson Laboratories) at a concentration of 5×10^11 GC/mouse. Request Quote

Research Field: diabetes

AAV Serotype: AAV8

Dose: 5×10^11 GC/mouse

Animal or cell line strain: 4-week-old female NOD mice


Transplanting human stem cell-derived islets (SC-islets) is a promising therapy for insulin-dependent diabetes. While functional SC-islets have been produced for clinical application, immune rejection by the host remains a challenge. Present attempts, including chronic immunosuppression and/or physical encapsulation, have some disadvantages. Here we explore a strategy to induce an immune-tolerant environment based on the immune privilege observed in the male gonad. Sperm appears after the maturation of the immune system and development of systemic self-tolerance and the testis protects these autoreactive germ cells by the physical structure of blood-testis-barrier (BTB) and active local immunosuppression. Human SC-islets transplanted into the mouse testis can be physically protected by the BTB and we find that the testis secretes cytokines that induce a population of regulatory T cells (Tregs) that express both CD4 and CD8. We identified cytokines secreted by testis and used a cocktail of IL-2, IL-10, and TGF-β for in vitro co-culture and in vivo transplantation demonstrating improved survival of SC-islets and the induction of Tregs.

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