Limb xenotransplantation using FK506 and RS61443 immunosuppression.
A new model of limb xenotransplantation has been developed to determine whether the newer immunosuppressive agents, FK-506 and RS-61443, either alone or in combination, can delay the rejection of a composite limb xenograft from donor Golden Syrian hamsters to recipient Lewis rats. Using a short-term course of immunosuppression for 14 days post-transplant, both FK-506 2 mg/kg/day and RS-61443 30 mg/kg/day were able to delay rejection. FK-506-treated animals had a mean rejection time of 10.2 days and RS-61443-treated animals had a mean rejection time of 10 days, compared with a mean rejection time of 6.4 days in non-immunosuppressed controls. Combination and sequential immunosuppression with both FK-506 and RS-61443 did not produce any improvement, compared with single-agent immunosuppression, and were quite toxic. Histologically, FK-506 seemed to prevent signs of rejection in the skin and muscle components of the limb xenograft better than RS-61443.
Hebebrand
D
D
UCLA Hand Center, Department of Orthopedic Surgery, University of California, Los Angeles 90095, USA.
Jones
N F
NF
Zohman
G
G
Rao
U
U
Soleiman
N
N
D000818:Animals; D006224:Cricetinae; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006614:Hindlimb / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008647:Mesocricetus; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus