Ferret Lung Transplant: An Orthotopic Model of Obliterative Bronchiolitis

H Sui; A. K Olivier; J. A Klesney-Tait; L Brooks; S. R Tyler; X Sun; A Skopec; J Kline; P. G Sanchez; D. K Meyerholz; N Zavazava; M Iannettoni; J. F Engelhardt; K. R Parekh

doi:10.1111/j.1600-6143.2012.04337.x

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Ferret Lung Transplant: An Orthotopic Model of Obliterative Bronchiolitis

Journal article

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Ferret Lung Transplant: An Orthotopic Model of Obliterative Bronchiolitis

H Sui, A. K Olivier, J. A Klesney-Tait, L Brooks, S. R Tyler, X Sun, A Skopec, J Kline, P. G Sanchez, D. K Meyerholz, …

American journal of transplantation, Vol.13(2), pp.467-473

02/2013

DOI: 10.1111/j.1600-6143.2012.04337.x

PMCID: PMC3638989

PMID: 23205765

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Abstract

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 fibrosis-associated 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.

lung

Bronchiolitis obliterans

chronic rejection

lung transplant

Details

Title: Subtitle: Ferret Lung Transplant: An Orthotopic Model of Obliterative Bronchiolitis
Creators: H Sui - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA
A. K Olivier - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA
J. A Klesney-Tait - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA
L Brooks - Department of Cardiothoracic Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA
S. R Tyler - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA
X Sun - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA
A Skopec - Department of Cardiothoracic Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA
J Kline - Department of Cardiothoracic Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA
P. G Sanchez - Department of Cardiothoracic Surgery, University of Maryland, Baltimore, MD
D. K Meyerholz - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA
N Zavazava - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA
M Iannettoni - Department of Cardiothoracic Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA
J. F Engelhardt - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA
K. R Parekh - Department of Cardiothoracic Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA
Resource Type: Journal article
Publication Details: American journal of transplantation, Vol.13(2), pp.467-473
DOI: 10.1111/j.1600-6143.2012.04337.x
PMID: 23205765
PMCID: PMC3638989
NLM abbreviation: Am J Transplant
ISSN: 1600-6135
eISSN: 1600-6143
Grant note: R37 DK047967 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK R01 DK047967 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK P30 DK054759 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK K08 HL114725 || HL / National Heart, Lung, and Blood Institute : NHLBI
Language: English
Date published: 02/2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pulmonary, Critical Care, and Occupational Medicine; Occupational and Environmental Health; Anatomy and Cell Biology; Pathology; Surgery; Radiation Oncology; Cardiothoracic Surgery; Internal Medicine
Record Identifier: 9984025351702771

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