1. Transplantation of NIT-1 cells with ectopic FADDdel-GFP expression for treatment of streptozotocin-induced diabetes.
- Author
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Hu P, Wang G, Wu S, Zhu H, Ping L, Wang C, and Shen G
- Subjects
- Animals, Apoptosis, Fas Ligand Protein antagonists & inhibitors, Female, Insulinoma genetics, Mice, Mice, Inbred BALB C, Sequence Deletion, Transfection, Treatment Outcome, Tumor Cells, Cultured, fas Receptor antagonists & inhibitors, Diabetes Mellitus, Experimental therapy, Fas-Associated Death Domain Protein genetics, Fas-Associated Death Domain Protein metabolism, Fas-Associated Death Domain Protein therapeutic use, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Green Fluorescent Proteins therapeutic use, Insulinoma metabolism, Islets of Langerhans Transplantation methods, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Recombinant Fusion Proteins therapeutic use
- Abstract
Islet transplantation is considered a therapeutic option for type 1 diabetes (T1D). However, allorejection is one major barrier for the successful islet transplantation. In the present study, we have tested the feasibility of a deletion construct for Fas-associated death domain protein (FADD; without the death effecter domain) fused with green fluorescent protein (FADDdel-GFP) for blocking the Fas-FasL signaling pathway in prevention of transplanted beta cell destruction by allo-rejection in T1D. In vitro studies have shown that NIT-1 cells with ectopic FADDdel expression were resistant to cytokine-induced apoptosis and CTL-mediated lysis. Diabetic Balb/c mice reached normoglycemia promptly and gained weight after transplantation of NIT-1 cells with ectopic FADDdel-GFP expression. These recipients showed a significant longer survival time than that of recipients transplanted with NIT cells with ectopic GFP expression only. Our results together suggest that FADDdel could be a useful target for the improvement of islet transplantation for T1D.
- Published
- 2009
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