Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice.
Allogeneic transplantation of islets of Langerhans was facilitated by the cotransplantation of syngeneic myoblasts genetically engineered to express the Fas ligand (FasL). Composite grafting of allogeneic islets with syngeneic myoblasts expressing FasL protected the islet graft from immune rejection and maintained normoglycemia for more than 80 days in mice with streptozotocin-induced diabetes. Graft survival was not prolonged with composite grafts of unmodified myoblasts or Fas-expressing myoblasts. Islet allografts transplanted separately from FasL-expressing myoblasts into the contralateral kidney were rejected, as were similarly transplanted third-party thyroid allografts. Thus, the FasL signal provided site- and immune-specific protection of islet allografts.
Lau
H T
HT
Department of Pediatric Surgery, Children's Hospital of Philadelphia, University of Pennsylvania, 19104, USA.
Yu
M
M
Fontana
A
A
Stoeckert
C J
CJ
D000818:Animals; D017209:Apoptosis; D017690:Cell Transplantation; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D053222:Fas Ligand Protein; D005818:Genetic Engineering; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D016381:Islets of Langerhans Transplantation; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D011994:Recombinant Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014162:Transfection; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins