Animal models of <i>ex vivo</i> lung perfusion as a platform for transplantation research

Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir N.; Hayes, Don; Black, Sylvester M.; Whitson, Bryan A.

doi:10.5493/wjem.v4.i2.7

Cited by 38 publications

(32 citation statements)

References 46 publications

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“…Indeed, short duration is a weakness of currently used rat models in which uninjured perfusion does not generally exceed 30–120 min (Table 4) [17–25]. This is likely due to rodent lung greater brittleness relative to human or porcine organs and to their tendency to develop atelectasis or edema in a shorter time [8]. …”

Section: Discussionmentioning

confidence: 99%

“…Because of their appropriate human-like lung size, large animals, such as pigs, have been broadly used to exploit this system [6, 7]. While these models were crucial to improve specific technical skills, small animal models can offer better means to identify the pathophysiological bio-molecular changes associated with ex vivo perfusion [8]. This kind of information is needed as the mechanism(s) underlying beneficial effects of extracorporeal reconditioning on donor lungs are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos

et al. 2016

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Ex vivo lung perfusion (EVLP) is a promising procedure for evaluation, reconditioning, and treatment of marginal lungs before transplantation. Small animal models can contribute to improve clinical development of this technique and represent a substantial platform for bio-molecular investigations. However, to accomplish this purpose, EVLP models must sustain a prolonged reperfusion without pharmacological interventions. Currently available protocols only partly satisfy this need. The aim of the present research was accomplishment and optimization of a reproducible model for a protracted rat EVLP in the absence of anti-inflammatory treatment. A 180 min, uninjured and untreated perfusion was achieved through a stepwise implementation of the protocol. Flow rate, temperature, and tidal volume were gradually increased during the initial reperfusion phase to reduce hemodynamic and oxidative stress. Low flow rate combined with open atrium and protective ventilation strategy were applied to prevent lung damage. The videos enclosed show management of the most critical technical steps. The stability and reproducibility of the present procedure were confirmed by lung function evaluation and edema assessment. The meticulous description of the protocol provided in this paper can enable other laboratories to reproduce it effortlessly, supporting research in the EVLP field.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos

et al. 2016

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“…Human precision-cut lung slices (PCLS), an ex vivo model consisting of all relevant cell types in their microanatomical environment (de Kanter et al, 2002), are well-established in pharmacological testing (Sturton et al, 2008), analysis of allergic immune responses (Wohlsen et al, 2003) and studies of xenobiotic metabolism (Lauenstein et al, 2014). There is also emerging literature concerning the use of ex vivo lung perfusion as a tool for experimental research (Nelson et al, 2014). Originally developed to allow lungs to be assessed for their physiological and functional parameters prior to transplant, the technology is a powerful tool that enables isolated organ modification and evaluation, although it is currently applied only to small and large animal models due to limited access to human lungs.…”

Section: Ex Vivo Lung Modelsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

124

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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“…Rodent sized systems have been available for several years (Harvard Apparatus), and human sized chambers are also now available. Following the first demonstration of functional assessment of a human lung ex vivo[39], EVLP systems have now evolved into lung preservation systems[40] (eg. Organ Care System from Transmedics™, and XPS™ from XVIVO Perfusion) and are currently being evaluated in clinical trials of lung transplantation for their ability to prolong organ preservation and to recondition lungs that would normally be turned down for transplant[41, 42] (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Bioreactor Development for Lung Tissue Engineering

Panoskaltsis‐Mortari

2015

Curr Transpl Rep

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Rationale Much recent interest in lung bioengineering by pulmonary investigators, industry and the organ transplant field has seen a rapid growth of bioreactor development ranging from the microfluidic scale to the human-sized whole lung systems. A comprehension of the findings from these models is needed to provide the basis for further bioreactor development. Objective The goal was to comprehensively review the current state of bioreactor development for the lung. Methods A search using PubMed was done for published, peer-reviewed papers using the keywords “lung” AND “bioreactor” or “bioengineering” or “tissue engineering” or “ex vivo perfusion”. Main Results Many new bioreactors ranging from the microfluidic scale to the human-sized whole lung systems have been developed by both academic and commercial entities. Microfluidic, lung-mimic and lung slice cultures have the advantages of cost-efficiency and high throughput analyses ideal for pharmaceutical and toxicity studies. Perfused/ventilated rodent whole lung systems can be adapted for mid-throughput studies of lung stem/progenitor cell development, cell behavior, understanding and treating lung injury and for preliminary work that can be translated to human lung bioengineering. Human-sized ex vivo whole lung bioreactors incorporating perfusion and ventilation are amenable to automation and have been used for whole lung decellularization and recellularization. Clinical scale ex vivo lung perfusion systems have been developed for lung preservation and reconditioning and are currently being evaluated in clinical trials. Conclusions Significant advances in bioreactors for lung engineering have been made at both the microfluidic and the macro scale. The most advanced are closed systems that incorporate pressure-controlled perfusion and ventilation and are amenable to automation. Ex vivo lung perfusion systems have advanced to clinical trials for lung preservation and reconditioning. The biggest challenges that lie ahead for lung bioengineering can only be overcome by future advances in technology that solve the problems of cell production and tissue incorporation.

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Animal models of ex vivo lung perfusion as a platform for transplantation research

Cited by 38 publications

References 46 publications

Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos

Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Bioreactor Development for Lung Tissue Engineering

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