Cross-circulation for extracorporeal support and recovery of the lung

O’Neill, John D.; Guenthart, Brandon A.; Kim, Jin-Ho; Chicotka, Scott; Queen, Dawn; Fung, Kenmond; Marboe, Charles C.; Romanov, Alexander; Huang, Sarah X.L.; Lin, Chen‐Yong; Snoeck, Hans-Willem; Bacchetta, Matthew; Vunjak‐Novakovic, Gordana

doi:10.1038/s41551-017-0037

Cited by 48 publications

(72 citation statements)

References 56 publications

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“…Fluorescently labeled MSCs were delivered via intratracheal liquid instillation and subsequently imaged using the minimally invasive transpleural imaging approach developed in this study. To maintain the viability of the lungs during experiments, explanted lungs were supported using an ex vivo lung perfusion (EVLP) platform developed by our research group 14,49,50 (Fig. 7a, i - ii , Supplementary Video 11).…”

Section: Resultsmentioning

confidence: 99%

“…A liquid plug can be injected into smaller airways using a narrow tube (diameter: <1.8 mm), which can be inserted through the working port (diameter: 1.8 mm) of the bronchoscope. Our research team accomplishes plug injection using this bronchoscope both in the research and clinical settings 14 . In addition, smaller bronchoscopes (e.g., device diameter: 3.1 mm, working channel diameter: 1.2 mm) could be used to improve access to even smaller airways in the human lungs 51 .…”

Section: Resultsmentioning

confidence: 99%

“…The lungs were prepared and cannulated in a similar method as previously described 14,49 and placed on an EVLP system to be ventilated and perfused with Perfadex. The collection and use of human tissue for research received approval from the Institutional Review Board (IRB) at Columbia University and LiveOnNY organ donor network.…”

Section: Methodsmentioning

confidence: 99%

“…While lung transplantation is the only definitive option for patients with end-stage lung disease, regenerative medicine and tissue engineering have yet to provide a solution for the critical shortage of donor lungs 12,13 . Therefore, more effective strategies are needed to reduce the global burden of respiratory disease and alleviate the donor lung shortage 14 .…”

Section: Introductionmentioning

confidence: 99%

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Controlled delivery and minimally invasive imaging of stem cells in the lung

Kim

Guenthart

O’Neill

et al. 2017

Sci Rep

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Intratracheal delivery of stem cells into injured or diseased lungs can provide a variety of therapeutic and immunomodulatory effects for the treatment of acute lung injury and chronic lung disease. While the efficacy of this approach depends on delivering the proper cell dosage into the target region of the airway, tracking and analysis of the cells have been challenging, largely due to the limited understanding of cell transport and lack of suitable cell monitoring techniques. We report on the transport and deposition of intratracheally delivered stem cells as well as strategies to modulate the number of cells (e.g., dose), topographic distribution, and region-specific delivery in small (rodent) and large (porcine and human) lungs. We also developed minimally invasive imaging techniques for real-time monitoring of intratracheally delivered cells. We propose that this approach can facilitate the implementation of patient-specific cells and lead to enhanced clinical outcomes in the treatment of lung disease with cell-based therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Controlled delivery and minimally invasive imaging of stem cells in the lung

Kim

Guenthart

O’Neill

et al. 2017

Sci Rep

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“…To overcome these limitations, our group previously used a swine model of cross-circulation (XC) to establish a lung support system that extended normothermic extracorporeal support to 36 hours and enabled statistically significant ex vivo recovery of severely injured lungs. 12,13 The use of an XC system to achieve ex vivo lung recovery mimics the clinical setting where in situ recovery of marginal quality lungs is achieved in patients placed on extracorporeal membrane oxygenation support for several days after transplantation. [14][15][16] Motivated by this clinical practice, we hypothesize that extending the duration of extracorporeal support from hours to days could not only enable the recovery of damaged lungs not currently salvageable using EVLP systems but also enable investigation of bioengineering strategies to improve or personalize organs before transplantation.…”

mentioning

confidence: 99%

Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine

Hozain¹,

Tipograf²,

Pinezich³

et al. 2020

The Journal of Thoracic and Cardiovascular Surgery

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Objectives: Lung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to<24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using crosscirculation with conscious swine.Methods: A swine behavioral training program and custom enclosure were developed to enable multiday cross-circulation between extracorporeal lungs and recipient swine. Lungs were ventilated and perfused in a normothermic chamber for 4 days. Longitudinal analyses of extracorporeal lungs (ie, functional assessments, multiscale imaging, cytokine quantification, and cellular assays) and recipient swine (eg, vital signs and blood and tissue analyses) were performed.

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