Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

Lama, Vibha N.; Belperio, John A.; Christie, Jason D.; El–Chemaly, Souheil; Fishbein, Michael C.; Gelman, Andrew E.; Hancock, Wayne W.; Keshavjee, Shaf; Kreisel, Daniel; Laubach, Victor E.; Looney, Mark R.; McDyer, John F.; Mohanakumar, Thalachallour; Shilling, Rebecca A.; Panoskaltsis‐Mortari, Angela; Wilkes, David S.; Eu, Jerry P.; Nicolls, Mark R.

doi:10.1172/jci.insight.93121

Cited by 58 publications

(46 citation statements)

References 138 publications

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“…The translational relevance of the pre-clinical findings was confirmed by an increased iron content in human allograft endobronchial tissue and transplant bronchoalveolar lavage fluid. The orthotopic tracheal transplantation model is particularly useful to address the role of iron in allograft invasion because the iron concentration of the transplant can be modulated at the time of surgery and because the planar anatomy of the trachea favors an accurate quantitation of fungal invasion (12, 13, 18, 61, 62). …”

Section: Discussionmentioning

confidence: 99%

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

et al. 2018

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Invasive pulmonary disease due to the mold Aspergillus fumigatus can be life-threatening in lung transplant recipients, but the risk factors remain poorly understood. To study this process, we used a tracheal allograft mouse model that recapitulates large airway changes observed in patients undergoing lung transplantation. We report that microhemorrhage-related iron content may be a major determinant of A. fumigatus invasion and, consequently, its virulence. Invasive growth was increased during progressive alloimmune-mediated graft rejection associated with high concentrations of ferric iron in the graft. The role of iron in A. fumigatus invasive growth was further confirmed by showing that this invasive phenotype was increased in tracheal transplants from donor mice lacking the hemochromatosis gene (Hfe−/−). The invasive phenotype was also increased in mouse syngrafts treated with topical iron solution and in allograft recipients receiving deferoxamine, a chelator that increases iron bioavailability to the mold. The invasive growth of the iron-intolerant A. fumigatus double-knockout mutant (ΔsreA/ΔcccA) was lower than that of the wild-type mold. Alloimmune-mediated microvascular damage and iron overload did not appear to impair the host’s immune response. In human lung transplant recipients, positive staining for iron in lung transplant tissue was more commonly seen in endobronchial biopsy sections from transplanted airways than in biopsies from the patients’ own airways. Collectively, these data identify iron as a major determinant of A. fumigatus invasive growth and a potential target to treat or prevent A. fumigatus infections in lung transplant patients.

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Section: Discussionmentioning

confidence: 99%

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

et al. 2018

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“…One of the many challenges in uncovering cellular and molecular mechanisms contributing to allograft dysfunction in lung transplantation has been the lack of animal models that adequately mimic the human scenario. For example, achieving a reproducible animal model to study obliterative bronchiolitis, a manifestation of chronic allograft rejection in lung transplant recipients, remains challenging, though some progress has recently been made (6 tantly, the authors show that two ligandreceptor pathways known to be important for the generation of antibody, the CD40 ligand/CD40 and CXCR5/CXCL13 pathways, are critical for the generation of DSA and pulmonary AMR pathology. For these reasons, the study by Li et al represents an exciting step forward in the field and is a platform for the development of potential novel therapies for pulmonary AMR that may have a substantial translational impact in lung transplant recipients.…”

Section: Retransplantation Of Foxp3 +Depleted Lung Allografts: Model mentioning

confidence: 99%

Foxp3+ T lymphocytes: immune regulators within the lung allograft

Lendermon¹,

McDyer²

2018

Journal of Clinical Investigation

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“…We aimed to evaluate the benefit of supplementation by HEMO 2 life V R to the most common lung preservation solution Perfadex V R in a well-recognized single-lung allo-transplantation model in pig [18].…”

Section: Introductionmentioning

confidence: 99%

Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO₂life^®in pig lung transplantation model

Glorion

Polard

Favereau

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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We describe the results of adding a new biological agent HEMOlife to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMOlife is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex) was compared with Perfadex associated with HEMOlife and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMOlife group led to significant improvement in functional parameters: reduction of graft vascular resistance (p < .05) and increase in graft oxygenation ratio (p < .05). Several ischemia-reperfusion related biomarkers showed positive trends in the HEMOlife group: expression of HMG B1 in serum tended to be lower in comparison (2.1 ± 0.8 vs. 4.6 ± 1.5) with Perfadex group, TNF-α and IL-8 in BALF were significantly higher in the two experimental groups compared to control (p < .05). During cold ischemia, expression of HIF1α and histology remained unchanged and similar to control. Supplementation of the Perfadex solution by an innovative oxygen carrier HEMOlife during hypothermic static preservation improves early graft function after prolonged cold ischemia in lung transplantation.

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Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

Cited by 58 publications

References 138 publications

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

Foxp3+ T lymphocytes: immune regulators within the lung allograft

Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO₂life^®in pig lung transplantation model

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Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

Cited by 58 publications

References 138 publications

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

Foxp3+ T lymphocytes: immune regulators within the lung allograft

Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life®in pig lung transplantation model

Contact Info

Product

Resources

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Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO₂life^®in pig lung transplantation model