Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs

Hozain, Ahmed E.; O’Neill, John D.; Pinezich, Meghan R.; Tipograf, Yuliya; Donocoff, Rachel; Cunningham, Katherine; Tumen, Andrew; Fung, Kenmond; Ukita, Rei; Simpson, Michael T.; Reimer, Jonathan A.; Ruiz, Edward C.; Queen, Dawn; Stokes, John W.; Cardwell, Nancy L.; Talackine, Jennifer; Kim, Jin-Ho; Snoeck, Hans-Willem; Lin, Chen‐Yong; Romanov, Alexander; Marboe, Charles C.; Griesemer, Adam; Guenthart, Brandon A.; Bacchetta, Matthew; Vunjak‐Novakovic, Gordana

doi:10.1038/s41591-020-0971-8

Cited by 62 publications

(78 citation statements)

References 86 publications

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“…Animals that are essential in COVID-19 research include ferrets, non-human primates, pigs and rodents [ 4 , 7 ]. These animals are used to understand transmission and to identify potential treatments.…”

Section: Main Textmentioning

confidence: 99%

How the COVID-19 pandemic highlights the necessity of animal research

et al. 2020

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Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for both animal welfare and researchers, advances on alternative methods have not progressed enough to be able to replace animal research in the foreseeable future. This trend has led first and foremost to a substantial increase in the administrative burden and hurdles required to make timely advances in research and treatments for human and animal diseases. The current COVID-19 pandemic clearly highlights how much we actually rely on animal research. COVID-19 affects several organs and systems, and the various animal-free alternatives currently available do not come close to this complexity. In this Essay, we therefore argue that the use of animals is essential for the advancement of human and veterinary health.

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Section: Main Textmentioning

confidence: 99%

How the COVID-19 pandemic highlights the necessity of animal research

et al. 2020

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“…A recent interesting study highlights an important aspect of the hypothesis. Lung function from rejected lung organ donors improved in function after inserting them in pigs [18] Here it is submitted that the donor lung in an OSO that has lost its variability (the brain dead donor) was dysfunctional and its reintroduction into the normal chemocline of the pig improved function. The above interactions suggest a role for the OSO as an indicator of health and disease.…”

Section: Is the Oscillator Hormetic In Nature And Could It Signal Heamentioning

confidence: 99%

The Status of An Inversely Coupled Oxic/Sulphidic Oscillator (OSO) in the Whole Body Chemocline Will Determine Clinical Unfolding in Systemic Inflammatory Response Syndrome (SIRS)* of Any Aetiology

Thangaraj¹

2020

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Life evolved in an euxinic world with subsequent oxic 'invasion' leading to two parallel but interconnected biospheres, hydrogen sulphide (H2S) and hydrogen peroxide (H2O2) exemplify these worlds respectively. Their concentration gradients have informational value in meromictic lakes. Similarly, it is posited, there exists a whole body chemocline in humans in which the two molecules form an inversely coupled oxic/sulphidic oscillator (OSO). The OSO is hormetic and characterised by a range of amplitudes and frequencies in health. Deviations from its baseline profile heralds the onset of SIRS before the appearance of clinical signs. Loss of oscillator status and transition to a steady state causes widespread intercellular and inter-organ communication failure presaging multi-organ dysfunction. The salient clinico-pathophysiological features of SIRS of any aetiology are emergent phenomena related to the OSO profile. Extent of recovery of organ function will mirror the recovery of the OSO profile thereby providing a tool to predict outcomes in SIRS.

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“…The higher length of physiologic lung support allows proper assessment of the lung graft and investigation of bioengineering strategies to improve lungs before transplantation with therapeutic interventions (e.g., gene or cell therapies). Therefore, XC can serve as a complementary solution to clinical EVLP to restore damaged donor lungs that could not otherwise be used for transplantation, as well as a translational testing tool for immunomodulation and advanced organ bioengineering (Hozain, O'Neill, et al, 2020).…”

Section: Ex Vivo Lung Perfusion Systemsmentioning

confidence: 99%