April 2018
A special thanks to this month's contributors: Professor Gloria Elliott, Dr. Peter Kilbride, Dr. Krishnaa Mahbubani, Dr. Bradley Weegman, Dr. Alireza Abazari, and Dr. Kate Franz
Edited by Dr. Alyssa Ward
Email alyssa.ward@organpreservationalliance.org with news, comments, or questions about the Briefings.
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The Organ Preservation Alliance partnered with Dr. David Klassen, Chief Medical Officer of the United Network for Organ Sharing, to explore the potentially wide-reaching social, eonomic, and policy implications of organ preservation advances. The open access article is available here ahead of print.
OPA is hosting a roundtable on 'Early applications of viable, functional tissue cryobanking.' The session will be held on Thursday, May 24th from 12:15-1:15 at the ISBER Annual Meeting in Dallas. Sign up won't be available until the conference, but space is limited, so email alyssa.ward@organpreservationalliance.org if you're interested in attending or contributing ideas for the session.
As announced last month, OPA is co-organizing a workshop on ex vivo organ perfusion with the American Society of Transplantation's Organ and Tissue Preservation Community of Practice. This workshop will take place on Monday, June 4th at the American Transplant Congress in Seattle. Contact alyssa.ward@organpreservationalliance.org for more information.
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Recent papers that caught the eye of our multi-institute Organ Banking Journal Club. If you're interested in joining, contact alyssa.ward@organpreservationalliance.org to learn more!
Globally, tens of thousands of people are in need of a liver transplant, but despite this growing need, thousands of donated livers are discarded each year. This is in part due to the inability to evaluate high-risk livers from donors with other health complications or donors whose hearts stopped beating. Conventional cold storage of organs slows cellular metabolism to preserve the organ but also limits functional assessment.
In a randomized trial of 220 liver transplants published in Nature this month (Nasralla, et al.) , researchers tested an alternative to cold storage, normothermic machine perfusion. The device, made by OrganOx, perfuses the liver with oxygenated blood and nutrients while maintaining the organ at body temperature, 37°C. Transplanted livers maintained on the device showed 50% lower level of biomarkers associated with injury and had a 50% lower rate of discard. Further analysis of the results suggests that livers from the high-risk donors whose hearts stopped beating had better outcomes than donor organs in cold storage and lower risk donors on machine perfusion.
A second study (Warnecke, et al.) was also published this month assessing the effect of preservation with machine perfusion, this time in lungs. They found preserving lungs on the Organ Care System Lung device (TransMedics) was as safe and effective as cold storage and had lower incidence of severe complications following transplant.
Machine perfusion is not only an important step towards expanding the donor pool and ending the organ shortage, but observing organ functionality in real time and making clinical decisions opens the door for more other advances, like rehabilitating organs, possibly synergizing with emerging gene therapies, drugs and other technologies.
More news coverage from Nature can be found here, including comments from the Organ Preservation Alliance. - Dr. Kate Franz
When freezing a cell suspension in cryoprotectant, the simplest goal is to enable cells to survive cold storage - generally by preventing harmful interactions between the ice and cells. To this end, optimization depends on understanding the behaviors of the components during the freezing process. Easier said than done, imaging these interactions requires high resolution through space and time that has proven difficult to achieve.
In Science this month, Dedovets, et al. report an approach using confocal microscopy to visualize oil droplets moving through water in a temperature gradient. Since the oil is not soluble in water, the droplets move through the freezing water analogously to cells. By fluorescently labeling the water and oil separately, the authors were able to semi-quantitatively capture behavior of the emulsion through space, time, and solute concentration.
When the oil droplets initially encounter the solidification front (the interface where water meets ice), they can be either rejected or engulfed. As engulfment can damage cells during cryopreservation, it is critical to optimize solute concentration and homogeneity to maximize cell rejection. As expected, slower cooling rates resulted in more droplet agglomerates rejected from - and even ‘surfing’ on the solidification front. Video of these results is available here. - Dr. Alyssa Ward
Skin can be used to treat burns and open wounds, in plastic surgery, and even for drug testing. Skin viability declines rapidly during preservation, losing growth factors and other proteins that may aid wound healing and are critical to judging whether a topical product is safe for humans. Further, viable preservation approaches for skin may be adapted to composite tissues, making life-changing limb and face transplants more accessible to the hundreds of thousands of people living with limb loss or severe facial defects.
Ibrahim, et al. sought to determine whether the quality of cryopreserved skin could be improved by the addition of an antifreeze protein (AFP) that has been shown to inhibit the growth of ice crystals. In a murine model of skin transplantation, there was more damage to the epidermis and dermal-epidermal junction in glycerol preserved grafts than those preserved with AFP.
The biomechanical properties of skin preserved with AFP were no worse than the glycerol-preserved grafts, so further work could determine whether other AFPs or other cryoprotective agents may be more potent preservatives. - Dr. Alyssa Ward
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