Living swine to maintain donor organs

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Science Translational Medicine  29 Jul 2020:
Vol. 12, Issue 554, eabd3628
DOI: 10.1126/scitranslmed.abd3628


Use of xenogeneic cross-circulation recovered injured human lungs and expand the pool of donor organs in lung transplantation.

Lung transplantation is a potentially life-saving therapy for patients with end-stage lung disease but remains underutilized due to scarcity of donor organs. Lungs are susceptible to injury before donation from insults such as aspiration, ventilatory trauma, and ischemia, which contribute to them being the least recovered organ from multiorgan donors. In an effort to increase available organs, transplant centers increasingly use ex vivo lung perfusion (EVLP) as a means of expanding the donor pool. EVLP is a technique in which lungs are perfused and ventilated on an extracorporeal circuit for a few hours to extend the period for evaluating marginal quality organs. Lungs with substantial injury often develop a progressive cycle of increasing edema, decreasing compliance, and worsening gas exchange leading to organ failure. The inability to maintain organs for prolonged periods or resuscitate more severely injured organs is a key hurdle to overcome for EVLP to markedly affect donor lung availability.

Hozain et al. describe an innovative approach to resuscitating donor organs that may unlock the potential of EVLP. Rather than relying on isolated mechanical perfusion systems with acellular or human blood-based perfusates, the authors pumped venous blood from a live swine to perfuse ex vivo human lungs while using a mechanical ventilator to provide gas exchange. They tested their cross-circulation approach on a combination of six sets of single and double human lungs rejected for use as transplant organs. Lungs were maintained in cold static storage for extended periods, longer than 24 hours in one case, before support on the swine cross-circulation circuit. Organs were treated with a clinical immunosuppression regimen augmented with cobra venom factor to further suppress the innate immune response. A control set of organs not receiving any immune suppression rapidly succumbed to hyperacute rejection, whereas the remaining test organs experienced a remarkable recovery despite the prolonged ischemic time before initiation of normothermic perfusion. Organs were maintained for an astounding 24 hours on the circuit, during which they experienced improved gas exchange and increasing compliance. Histopathology analysis demonstrated resolution of inflammation and edema with maintained cellular integrity.

Although the remarkable findings of Hozain and colleagues require study in more lungs and further understanding of the risks of zoonotic infections and exposure to xenoantigens before clinical use, their work envisages an exciting future for EVLP. Prolonged support enabled by the swine cross-circulation circuit may lead protocols to recover infected or injured organs currently not suitable for transplant. Additionally, insights from the living cross-circulation model inform how to advance mechanical EVLP systems through the addition of metabolic substrates and methods to maintain electrolyte balance and modulate the inflammatory response, which may solve the riddle of how to maintain ex vivo organs indefinitely. Hozain et al. have shown that perhaps we will not have to wait long before donor organ availability can be increased to reduce the suffering of patients with end-stage lung disease.

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