Transplantation of NIT-1 cells with ectopic FADDdel-GFP expression for treatment of streptozotocin-induced diabetes.
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.
Hu
Ping
P
Department of Microbiology and Immunology, Medical College of Jinan University, Guangzhou, 510632, People's Republic of China.
Wang
Guohua
G
Wu
Sha
S
Zhu
Huifen
H
Ping
Lei
L
Wang
Congyi
C
Shen
Guanxin
G
D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D017384:Sequence Deletion; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000037:antagonists & inhibitors
C505534:Fadd protein, mouse; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505658:Fasl protein, mouse; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D049452:Green Fluorescent Proteins