Obliterative airway disease in a porcine heterotopic bronchial allograft model.
Representative animal models are needed for the study of posttransplant obliterative bronchiolitis (OB). Because human OB originates in terminal bronchi, the validity of tracheal models can be questioned. Using our hetrotopic model, we implanted pieces of a lobar bronchus subcutaneously into domestic pigs. Five groups were included: autograft implants, allograft implants, allograft implants with 2 regimens of cyclosporine (CsA)azathioprine (AZA)-methylprednisolone (MP), and allograft implants with CsA-SDZ RAD-MP. Samples were harvested at 2 weeks and at 1, 2, and 3 months. The histological findings were graded from 0 to 3. Following initial ischemic epithelial damage, autograft implants recovered, but untreated allografts and those treated with CsA-AZA-MP were totally and permanently damaged within one month. In the group treated with CsA-SDZ RAD-MP, a maximal grade 1.5 +/- 0.5 epithelial injury was seen at one month. Epithelial damage preceded and correlated with luminal obliteration. The obliterative lesions histologically resembled human OB. Differences from our previous findings with terminal bronchioles were minor. This study supports the use of larger-size airways in the study of OB.
Department of Medicine, University of Helsinki, Helsinki University Central Hospital, Finland. paula.maasilta@helsinki.fi
P
P
Maasilta
U S
US
Salminen
E
E
Taskinen
E M
EM
Hietala
T
T
Ikonen
A
A
Harjula
D000818:Animals; D001980:Bronchi / Q000473:pathology / Q000637:transplantation*; D001989:Bronchiolitis Obliterans / Q000601:surgery*; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013552:Swine; D014182:Transplantation, Autologous / Q000276:immunology / Q000473:pathology / Q000502:physiology; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology / Q000502:physiology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine