June 2018
 
 
 

A special thanks to this month's contributors: 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.

Click here to see the past Biopreservation Briefings!

 
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OPA welcomes new members of the Advisory board

We are expanding our scientific advisory board to reflect the ongoing contributions of James Markmann (Chief of Transplantation, Massachusetts General Hospital), Lori West (Director, Canadian National Transplant Research Program and Alberta Transplant Institute), Zisis Kozlakidis (Head, Laboratory Services and Biobanking (IARC/WHO) and ISBER Past-President), Kevin Myer (President and CEO, LifeGift), Susan Gunderson (CEO, LifeSource), Jayan Nagendran (Vice President and Director of Clinical Investigation, Tevosol; Surgeon and Director of Research, Division of Cardiac Surgery, University of Alberta), Gina Dunne Smith (Executive Director, International Institute for the Advancement of Medicine), David Hartell (Executive Director, Canadian National Transplant Research Program), and  Matthew Wadsworth (VP of Clinical Affairs, Nevada Donor Network). We look forward to continuing to work together towards our common goals!

 

Join us for CRYO2018 organ preservation sessions!

Following the successful 2017 Organ Banking Summit, the Organ Preservation Alliance is hosting several sessions at the upcoming CRYO2018 meeting July 10-13th in Madrid, Spain. The "mini-Organ Banking Summit" sessions will explore recent advances and remaining challenges in cryopreservation of organs and tissues, including a plenary session on the possibilities that organ cryopreservation could enable for the field of organ transplantation.

All sessions will be held July 11th in the Central building:

9:20am  Plenary Session: Cryopreservation of Organs 1

2:00pm Symposium 6: Cryopreservation of Reproductive Tissue for Cancer Survivors: Clinical and Research Perspectives

4:30pm Symposium 7: Cryopreservation of Organs 2

 

Click here for more information and registration for CRYO2018.

 

Big changes in the American Society of Transplantation Community of Practice

In 2016, we launched a Community of Practice (COP) with the American Society of Transplantation. The response has been so enthusiastic that we have recently expanded from the Organ and Tissue Preservation COP to the  Recovery and Preservation COP (RAP COP), formally representing the organ procurement community. Jedd will continue to chair the COP and Korkut Uygun, PhD has become the new co-chair. The Executive Committee now includes  Alexandra Glazier, JDSebastian Giwa, PhD, MBASusan Gunderson, MHA, and Joseph Ferreira, MBA

The newly rebranded RAP COP gathered at the American Transplant Congress this year for a productive conversation about the progress in ex situ organ perfusion and the pathways to expanded clinical implementation of these technologies. Many of our speakers are quoted in this Nature Biotechnology editorial, which gives an excellent overview of ex situ perfusion technology development and the research pushing the field forward. We'll continue to engage the perfusion community moving forward - email alyssa.ward@organpreservationalliance.org if you're interested in getting involved.

 

Exploring the possibilities for viably preserved tissues

OPA hosted a roundtable discussion of 'Early applications of viable, functional tissue cryobanking' at the ISBER annual meeting in Dallas in May. This productive conversation focused on the analyses enabled by viable preservation and the barriers to implementing new technologies in biobanks. Some promising applications include patient-derived xenografts, establishing primary cell lines, fresh and diseased brain tissue for neuroscience research, and tissues and tumors from rare diseases. Thank you to ISBER leadership for hosting an amazing conference and ISBER members for sharing your insights with us!

 
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OPA Welcomes Mitch Rostad

Mitch is a fourth year medical student at Emory University with a background in consulting and nonprofit development who is taking a year to work with OPA as our first ever Research Fellow before starting residency. His interest in transplantation includes the intersection of emergency preparedness and preservation. He has volunteered with OPA for several years and we're excited to have him join us full time!

 

Does reading all this make you want to join the team?

The Organ Preservation Alliance is planning to add a least one more Program Director to our full-time staff! If you're hard-working, excited about preservation, and in the Berkeley, CA area, email alyssa.ward@organpreservationalliance.org with a resume and paragraph of interest.

 
 
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Jump to: OPA updates or News from our network

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!

 

Bioengineering viably preserved liver slices

In biomedical research, testable liver tissue is especially valuable as it provides a method to test drug metabolism in human tissue. Monolayer cells isolated from healthy livers that could not be transplanted have become the conventional model for drug testing. An alternative approach involves encapsulating cells in an elastic polymer structure with a high water content to form 3D tissue engineered liver slices (TELS) that maintain the functional and morphological characteristics of intact liver tissue.

While the high water content makes TELS particularly valuable as experimental models, it also makes them prone to ice crystallization during cryopreservation, and of course, the resulting damage. Chen et al. developed an approach to generate TELS that could be cryopreserved for up to 10 days and recover viability and liver-specific functions in culture by about 10 days after thawing. TELS that had been frozen also maintained responsiveness to a growth factor inhibitor, suggesting they could be used for drug testing after preservation. After nearly two weeks, there was greatly reduced cell viability, however the 10 days of preservation represents a promising step towards off-the-shelf drug testing solutions.

 

Mechanisms behind preservation improvements

Machine perfusion techniques have been shown to preserve livers donated after cardiac death better than traditional static cold storage (see e.g. Schlegel et al.). Key to improving and optimizing protocols is understanding treatment effects at the molecular level. To that end, He et al. examined the effects of hypothermic machine perfusion (HOPE) in a rat model of liver donation after cardiac death. While traditional organ cooling resulted in damage due to inflammation and oxidation, HOPE inhibited a key pathway activated in these damaging responses, reducing tissue injury.

Using the same disease model, Xue et al. found hypothermic machine perfusion maintained the levels of a transcription factor regulating an important antioxidant pathway that is downredulated during conventional cold storage. There was concurrent reduction in organ damage after reperfusion in perfused livers.

These two groups used differing perfusion conditions, which may involve different pathways in the prevention of injury, however it is also possible that machine perfusion activates multiple pathways that work in concert to decrease inflammation. Other groups have also examined the molecular changes during e.g. lung perfusion and steatotic liver perfusion, contributing important insights to our understanding of machine perfusion.

 

Small RNAs have a big impact on freeze tolerance

 

Freeze tolerance is not uncommon in the animal world, with the wood frog representing a well-studied system that can freeze over half of its body water for months with no measurable brain activity. Hadj-Moussa and Storey found that the proteins that generate the small regulatory RNAs known as microRNAs were significantly decreased in frozen or thawed frog brains (as compared to control brains).

Accordingly, there was a decrease in over one-third of the 113 microRNAs assayed in frozen or thawed frog brains. These microRNAs regulate key pathway components in DNA replication, intracellular signal transduction, and energy generation. Further study can determine whether these findings can be applied to crypreservation of freeze-intolerant tissues and whether these pathways used by the frog brain to prevent ischemic and other injuries could be relevant to preventing damage in human diseases, like stroke.

 
 
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Jump to: OPA updates or Selected publications

Help keep the community updated by sending your news to alyssa.ward@organpreservationalliance.org

 
  • Dr. Korkut Uygun investigated the mechanisms of steatotic liver recovery during sub-normothermic machine perfusion
  • Dr. Yoed Rabin demonstrated effects of polarized light on vitrification
  • Dr. Jason Acker showed that cryopreserved cells can be reliably used in a clinical assay that was previously limited to fresh samples
  • Dr. Kenneth Storey published on the role of lysine acetyltransferases in ground squirrel hibernation, the anoxia-induced reponse of a transcription factor, the stress response to dehydration, microRNA regulation of hypoxic changes, and as discussed in more depth above, looked for microRNAs that may protect brains from freeze-damage
 

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