Lung Transplantation in the Fischer 344→Wistar Kyoto Rat Strain Combination is Not Suitable to Study Bronchiolitis Obliterans

Hirschburger, Markus; Greschus, Susanne; Kuchenbuch, Tim; Plötz, Christian; Obert, Martin; Traupe, Horst; Padberg, Winfried; Grau, Veronika

doi:10.1016/j.healun.2007.01.018

Cited by 24 publications

(23 citation statements)

References 23 publications

(46 reference statements)

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“…Interestingly, the minor-mismatched allografts showed recovery of aeration along the course, suggesting that the relatively mild rejection process was overcome in this strain combination without leading to total necrosis as is seen in full MHC-mismatched allografts. This phenomenon is likely to be similar to that observed in minormismatched rat orthotopic lung transplantation (22,23). The model of minor-mismatched orthotopic lung transplantation from B10 to B6 mice has been developed as a model of OB associated with severe acute rejection (13).…”

Section: Discussionsupporting

confidence: 66%

Lentivirus IL-10 Gene Therapy Down-Regulates IL-17 and Attenuates Mouse Orthotopic Lung Allograft Rejection

Hirayama

Sato

Loisel-Meyer

et al. 2013

American Journal of Transplantation

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contributed equally to this work.The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 AE 0.6 vs. 2.0 AE 0.6 (mean AE SD); p ¼ 0.025; n ¼ 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-gt without affecting levels of IL-12 and interferon-g (IFNg). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation.

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Section: Discussionsupporting

confidence: 66%

Lentivirus IL-10 Gene Therapy Down-Regulates IL-17 and Attenuates Mouse Orthotopic Lung Allograft Rejection

Hirayama

Sato

Loisel-Meyer

et al. 2013

American Journal of Transplantation

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“…There are several animal models that have been used to study the biology of OB each with their advantages and drawbacks (18)(19)(20)(21)(22)(23). The widely used heterotopic murine tracheal transplant model does not reflect the clinical procedure of lung transplantation as the allograft is neither vascularized nor aerated (24).…”

Section: Discussionmentioning

confidence: 99%

290 Ferret Lung Transplant: An Orthotopic Model for Obliterative Bronchiolitis

Sui

Brooks

Klesney-Tait

et al. 2012

The Journal of Heart and Lung Transplantation

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Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosisassociated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB.

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“…Isogeneic lungs (LEW to LEW, F344 to F344, and WKY to WKY) were successfully transplanted under identical conditions by the same experimenters (Hirschburger and Grau) in the context of two other studies [16,17]. These animals survived, and graft histology remained almost normal.…”

Section: Lung Transplantationmentioning

confidence: 99%

“…Transplant morphology (F344 to WKY) was assessed by fpVCT as described previously [17,19]. In brief, the fpVCT is a prototype developed and manufactured by General Electric Global Research (Niskayuna, NY, USA).…”

Section: Flat-panel Volumetric Computed Tomographymentioning

confidence: 99%

See 1 more Smart Citation

Treatment with keratinocyte growth factor does not improve lung allograft survival in the rat

Hirschburger

Obert

Traupe

et al. 2008

Langenbecks Arch Surg

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Lung Transplantation in the Fischer 344→Wistar Kyoto Rat Strain Combination is Not Suitable to Study Bronchiolitis Obliterans

Cited by 24 publications

References 23 publications

Lentivirus IL-10 Gene Therapy Down-Regulates IL-17 and Attenuates Mouse Orthotopic Lung Allograft Rejection

Lentivirus IL-10 Gene Therapy Down-Regulates IL-17 and Attenuates Mouse Orthotopic Lung Allograft Rejection

290 Ferret Lung Transplant: An Orthotopic Model for Obliterative Bronchiolitis

Treatment with keratinocyte growth factor does not improve lung allograft survival in the rat

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