title: Low-dose immunosuppression in a rat hind-limb transplantation model.
abstract: Composite tissue allografts (CTAs) offer an alternative to conventional reconstructive methods. However, the toxicity of the drugs that are required to prevent rejection has prevented its widespread clinical application. The purpose of this study was to determine whether a low-dose, corticosteroid-free combination regimen of tacrolimus and mycophenolate mofetil (MMF) would prevent rejection in a rat hind-limb model, with minimal toxic side effects. Three groups were used in this study. In group I, Wistar Furth (WF) rats received a syngeneic WF hind-limb. In groups II and III, WF rats received an ACI hind-limb. The latter were treated with tacrolimus-MMF. Assessment for rejection, flow cytometry, and mixed lymphocyte reactions was performed. Biopsies were taken regularly and at the time of killing. Combination therapy with low-dose tacrolimus-MMF effectively prolonged CTA survival indefinitely, with minimal side effects. Toxicity associated with immunosuppressive drugs can be avoided in a low-dose combination corticosteroid-free regimen.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Louisville, 511 South Floyd Street, 320 MDR Building, Louisville, KY 40292, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Perez-Abadia
authors.forename: Luis
authors.initials: L
authors.lastname: Laurentin-Perez
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Gorantla
authors.forename: Cedric G
authors.initials: CG
authors.lastname: Francois
authors.forename: Marieke
authors.initials: M
authors.lastname: Vossen
authors.forename: Pascal C R
authors.initials: PC
authors.lastname: Brouha
authors.forename: Haldun I
authors.initials: HI
authors.lastname: Orhun
authors.forename: Gary L
authors.initials: GL
authors.lastname: Anderson
authors.forename: Claudio
authors.initials: C
authors.lastname: Maldonado
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Pidwell
authors.forename: Warren C
authors.initials: WC
authors.lastname: Breidenbach
authors.forename: John H
authors.initials: JH
authors.lastname: Barker
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy*; D006614:Hindlimb / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus