TY - JOUR
T1 - Low-dose immunosuppression in a rat hind-limb transplantation model
AU - Perez-Abadia, Gustavo
AU - Laurentin-Perez, Luis
AU - Gorantla, Vijay S.
AU - Francois, Cedric G.
AU - Vossen, Marieke
AU - Brouha, Pascal C.R.
AU - Orhun, Haldun I.
AU - Anderson, Gary L.
AU - Maldonado, Claudio
AU - Pidwell, Diane J.
AU - Breidenbach, Warren C.
AU - Barker, John H.
N1 - Funding Information:
Acknowledgements The work described here was funded in part by grants from the Jewish Hospital Foundation, Louisville, Kentucky, USA. We would like to thank Lynn Ogden, MD, Mukunda B. Ray, MD, PhD, and Gordon Wang, MD, for their contribution in the preparation and analysis of histological sections, and Anthony Jevans, PhD, for his contribution in the blood analysis. We would also like to thank the animal facility staff for their outstanding animal care.
PY - 2003/12/1
Y1 - 2003/12/1
N2 - 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.
AB - 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.
KW - Combination therapy
KW - Composite tissue allografts
KW - Mycophenolate mofetil
KW - Rats
KW - Tacrolimus
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U2 - 10.1007/s00147-003-0576-4
DO - 10.1007/s00147-003-0576-4
M3 - Article
C2 - 12904844
AN - SCOPUS:0346257963
VL - 16
SP - 835
EP - 842
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 12
ER -