Effects of immunosuppressive treatment on host responses against intracerebral porcine neural tissue xenografts in rats

Background. Embryonic xenogeneic neural tissue is an alternative for transp lantation in Parkinson's disease, but immune responses limit the applicatio n. The aims of this study were to enhance the in vitro viability rates by d onor tissue pretreatment; to compare the efficacy of cyclosporine A (CsA) a nd tacrolimus (FK) in inhibiting xenograft rejection in rats; to evaluate a dditional inductive therapy with prednisolone (PRE) or mycophenolate mofeti l (MMF), Methods. Tirilazad (a lipid peroxidase inhibitor) or FK and acYVAD-cmk (a c aspase inhibitor), were added to embryonic porcine ventral mesencephalic ti ssue and viability was assessed in vitro. Tirilazad-treated tissue was graf ted to the striatum of rats that were either left untreated or immunosuppre ssed with FK (1 mg/kg) or CsA (15 mg/kg) alone or in combination with a 2-w eek PRE (20 mg/kg) or MMF (40 mg/kg) induction course. Xenograft survival a nd host responses were determined using immunohistochemistry. Results. Pretreatment with tirilazad enhanced tissue survival in vitro. Aft er transplantation into untreated controls, there was no graft survival at twelve weeks, Neural cell counts were significantly improved in immunosuppr essed recipients, but there were no differences between the treatment group s. Additional inductive treatment reduced the infiltration with CD4+ and CD 8+ cells, and macrophage infiltration was reduced compared with animals giv en CsA or FK alone. Conclusion. Pretreatment of the donor tissue with free-radical scavengers r educes cell loss caused by tissue trauma. Porcine neural tissue xenografts survive significantly better in animals immunosuppressed with either FK or CsA. Additional inductive treatment with PRE or MMF reduced the infiltratio n of host cells into the xenografts.