Et. Ustuner et al., Long-term composite tissue allograft survival in a porcine model with cyclosporine/mycophenolate mofetil therapy, TRANSPLANT, 66(12), 1998, pp. 1581-1587
Background. Low-dose cyclosporine (CsA)/mycophenolate mofetil (MMF) therapy
has significantly reduced the frequency of rejection and drug-induced side
effects in rat hindlimb allograft recipients. With an eye toward direct cl
inical application, we developed a large-animal extremity composite tissue:
allograft model to assess the antirejection efficacy and systemic toxicity
of combination CsA/MMF treatment.
Methods. Radial forelimb osteomyocutaneous flap transplants were performed
between size-matched, outbred pigs assigned to one of two groups: 5 control
pigs received no immunosuppression, and 10 pigs received a once-daily oral
CsA/MMF/prednisone regimen. Rejection was assessed by visual inspection of
flap skin and correlated with serial histopathologic examination of skin b
iopsies.
Results. In all control pigs, the flap was completely rejected on day 7, Of
the 10 pigs receiving treatment, one died from pneumonia and an another fr
om an anesthetic complication on days 19 and 30, respectively, without sign
s of rejection. Two flaps were lost on days 25 and 29 from severe rejection
, Three pigs were free of rejection at the end of the 90-day follow-up peri
od, and three had stable mild-to-moderate rejection at 90 days (P = 0.0007
vs, controls). White blood cell and platelet counts, serum creatinine value
s, and liver function tests remained normal in all animals receiving immuno
suppressive therapy.
Conclusions. Our results, to our knowledge, demonstrate for the first time
that rejection can be significantly delayed in a large-animal composite tis
sue allograft model including skin using only orally administered agents do
sed according to clinically relevant strategies without significant drug-sp
ecific systemic side effects.