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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.
| Abbreviations | ||
| T1D | = | type 1 diabetes |
| GFP | = | green fluorescent protein |
| DED | = | death effective domain |
| DD | = | death domain |
| FADD | = | Fas-associated death domain protein |
| STZ | = | streptozotocin |
| Abbreviations | ||
| T1D | = | type 1 diabetes |
| GFP | = | green fluorescent protein |
| DED | = | death effective domain |
| DD | = | death domain |
| FADD | = | Fas-associated death domain protein |
| STZ | = | streptozotocin |