Lung Lavage and Surfactant Replacement During Ex Vivo Lung Perfusion for Treatment of Gastric Acid Aspiration–Induced Donor Lung Injury

Nakajima, Daisuke; Liu, Mingyao; Ohsumi, Akihiro; Kalaf, R.; Iskender, Ilker; Hsin, Michael; Kanou, Takashi; Chen, Manyin; Baer, Brandon; Coutinho, R.; Maahs, Lucas; Behrens, P.; Azad, S.; Martinu, T.; Waddell, Thomas K.; Lewis, James F.; Post, Martin; Veldhuizen, Ruud A. W.; Cypel, Marcelo; Keshavjee, Shaf

doi:10.1016/j.healun.2016.11.010

Cited by 69 publications

(48 citation statements)

References 28 publications

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“…Notably, following 36 h of XC there was no significant difference between the PaO 2 /FiO 2 of injured and control lungs, demonstrating that even severely injured lungs can be recovered using this methodology (Guenthart et al, 2019b). Additionally, previous studies utilizing EVLP (Inci et al, 2008;Meers et al, 2010;Khalifé-Hocquemiller et al, 2014;Nakajima et al, 2017) have investigated recovery of global lung function (e.g., compliance, gas exchange), but not the dynamic interplay between cellular metabolism, activity and regeneration of lungs while on extracorporeal support as with our XC platform.…”

Section: Ex Vivo Support and Recovery Of Lungs For Transplantmentioning

confidence: 85%

“…Over the years, EVLP used in research settings has enabled therapeutic cell delivery, airway lavage and surfactant replacement (Nakajima et al, 2017), and even the clearance and inactivation of hepatitis C virus (Galasso et al, 2019). While EVLP enables support and recovery of marginal-quality lungs up to 6 h (Cypel et al, 2011), the duration of lung support ex vivo is limited by the inability to provide the metabolic clearance and homeostatic physiologic environment of the lung, with its innate reparative mechanisms.…”

Section: Ex Vivo Support and Recovery Of Lungs For Transplantmentioning

confidence: 99%

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Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

Dorrello

Vunjak‐Novakovic

2020

Front. Bioeng. Biotechnol.

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The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment. With the current acceptance rate of donor lungs of only 20%, rescuing even one half of the rejected donor lungs would increase the number of transplantable lungs threefold, to 60%. We review recent advances in lung bioengineering that have potential to repair the epithelial and vascular compartments of the lung. Our focus is on the long-term support and recovery of the lung ex vivo, and the replacement of defective epithelium with healthy therapeutic cells. To this end, we first review the roles of the lung epithelium and vasculature, with focus on the alveolar-capillary membrane, and then discuss the available and emerging technologies for ex vivo bioengineering of the lung by decellularization and recellularization. While there have been many meritorious advances in these technologies for recovering marginal quality lungs to the levels needed to meet the standards for transplantation -many challenges remain, motivating further studies of the extended ex vivo support and interventions in the lung. We propose that the repair of injured epithelium with preservation of quiescent vasculature will be critical for the immediate blood supply to the lung and the lung survival and function following transplantation.

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Section: Ex Vivo Support and Recovery Of Lungs For Transplantmentioning

confidence: 85%

Section: Ex Vivo Support and Recovery Of Lungs For Transplantmentioning

confidence: 99%

Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

Dorrello

Vunjak‐Novakovic

2020

Front. Bioeng. Biotechnol.

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“…A variety of other therapies have been effective at recovering marginal grafts on EVLP. These include delivery of vasoconstrictors such as epinephrine, 107 bronchodilators, 108 and high-dose antibiotics 109 used to clear alveolar epithelial fluid, improve ventilation prior to transplantation, and clear infection in human donor lungs, respectively. Additionally, the Toronto Group administered IL-10 gene therapy to injured human lungs during 12 h of EVLP, and observed improved function indicated by arterial oxygen pressure and pulmonary vascular resistance in the treated group compared to the untreated control.…”

Section: Lungmentioning

confidence: 99%

Bioengineering approaches to organ preservation ex vivo

Pinezich

Vunjak‐Novakovic

2019

Exp Biol Med (Maywood)

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The advent of successful solid organ transplantation is undoubtedly among the most significant medical achievements of the 20th century. Despite advances in the field of transplantation since its inception over 50 years ago, our approach to donor organ preservation outside of the body remains unchanged. Recently, attempts have been made to replace static cold storage with more sophisticated ex vivo machine perfusion. Rather than cooling the organ on ice to slow metabolic processes, machine perfusion aims to support normal metabolic function in a near-physiologic environment and to provide a platform on which the organ can be evaluated, preserved, and recovered. Ex vivo machine perfusion devices have demonstrated early success with respect to transplant outcomes in heart, lung, and liver, with perfusion times limited to several hours. The continued development of more advanced perfusion systems is likely to extend the duration of ex vivo organ support to days or even weeks, and enable recovery of initially unsuitable donor organs. In this review, we discuss recent clinical and pre-clinical studies, state-of-the-art organ preservation technologies, existing limitations, and a perspective on future developments.

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“…An intensive research effort is also aimed at harnessing EVLP to treat donor lungs that are impaired in other ways. For example, it was shown that donor lungs impaired by aspiration of gastric acid can be treated with lavage and surfactant replacement during EVLP . Similarly, in the case of donor lung infection, antibiotics will be delivered in the EVLP system at high doses to avoid systemic toxicity .…”

Section: Long‐term Futurementioning

confidence: 99%

“…For example, it was shown that donor lungs impaired by aspiration of gastric acid can be treated with lavage and surfactant replacement during EVLP. 17 Similarly, in the case of donor lung infection, antibiotics will be delivered in the EVLP system at high doses to avoid systemic toxicity. 18 Other preclinical studies show that hepatitis C virus can be cleared from donor lungs using a combination of ultraviolet irradiation and photodynamic therapy during EVLP, similar to the means used in blood banks to sterilize donor blood components.…”

Section: Mid-term Futurementioning

confidence: 99%