September 2018
A special thanks to this issue's contributors: Dr. Peter Kilbride, Dr. Krishnaa Mahbubani, Dr. Bradley Weegman,
Dr. Alireza Abazari, Dr. Simona Baicu, Mitch Rostad, 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!
Jump to: Selected publications or News from our network
The recently expanded American Society of Transplantation Recovery and Preservation Community of Practice (RAP COP; expansion covered here) hosted the Timely Topics in Transplantation webinar this month on achieving immune tolerance in deceased organ donation.
Immune tolerance induction - often called the holy grail of transplantation - is based on the idea that we can train the body to recognize a transplanted organ as its own, preventing rejection without immunosuppression. Great progress has been made in living kidney transplantation, with promising trials in progress at leading institutions.
Click here to access the webinar archives and listen to Medawar Prize winner Dr. David Sachs discuss these trials with a focus on the next frontier: inducing tolerance in the context of deceased donor transplantation, the most common type of transplant in the U.S.
The American Society of Mechanical Engineers, the International Society for Cellular and Gene Therapy, the International Society for Biological and Environmental Repositories, and the Society for Cryobiology joined us in hosting a stakeholder roundtable on leveraging cryopreservation research to improve practices in cell therapy in Washington DC this past July.
Representatives from industry, academia, professional societies, regulatory and funding agencies participated in discussions about the regulatory processes, existing standards and best practices in cryopreservation, and identified gaps and areas for future investment. A huge thanks to ASME for their leadership during this event and to all the attendees for their willingness to share their expertise, past experiences, and ideas!
CRYO2018 brought together hundreds of the top preservation researchers to share progress and ideas. Among the sessions, we hosted a ‘mini-Organ Banking Summit’ to explore the recent advances and remaining challenges in organ and tissue cryopreservation, highlighting theoretical and applied work in vitrification, nanowarming, and slow freezing.
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!
One in ten deaths of children under 5 years old globally is due to diarrheal disease and this disproportionally affects children in developing countries. A study funded through the Bill and Melinda Gates Foundation (Kotloff et al., 2013) showed that the pathogen Cryptosporidium parvum was the second most prevalent cause of diarrheal disease and a significant source of childhood mortality. Research into Cryptosporidium therapies was identified as a key priority to reduce the worldwide burden of diarrheal disease.
A significant roadblock in the development of a therapy is the lack of a cryopreservation strategy for Cryptosporidium. Instead, the parasite must be maintained through constant propagation in calves, mice, and pigs. However, a recent study in Nature Communications (Jaskiewicz et al., 2018) made a significant advance by developing a protocol enabling cryopreservation of viable, infectious oocysts-- something which had been unsuccessfully attempted for the past 30 years.
The researchers made two important findings to develop this protocol. First, oocysts have a thick outer wall that must be permeabilized with bleach before CPAs are added. Second, once the inner sporozoites were dehydrated they could be frozen via ultrafast cooling (only slow freezing had been attempted previously). Importantly, after thawing the cryopreserved oocysts, they were able to establish infections in a mouse model, bringing researchers one step closer to an effective therapeutic agent. -Dr. Kate Franz
Supercooling is the idea that a liquid can be cooled below its freezing point without freezing. This phenomenon has even made it into popular culture, where people place a bottle of filtered water, free of impurities, into a freezer for a couple hours. The resulting water is colder than the normal freezing point of water, but still liquid until ice nucleates. Physical disruption can nucleate ice formation, but new work from Huang et al. suggests that contact with air is important to this process.
As the old adage says, you can’t mix oil and water. Researchers took advantage of this property to overlay water with oil and found that the oil prevented water from freezing, even down to -20°C and even when the tube was physically disturbed. They extended these findings to red blood cells in UW solution and found high viability and normal cell morphology after 100 days at -16°C. This represents more than twice the current standard preservation duration, which could offer a significant improvement to blood storage logistics. Cell therapy products represent another attractive opportunity to apply this finding, even before scaling to organ and tissue preservation. - Dr. Alyssa Ward
Over the past 50 years, the preservation of heart valves for clinical use has remained fundamentally unchanged despite issues around the expense of liquid nitrogen storage, inflammation, and long-term degeneration that ultimately leads to the need for replacement valves. Biermann et al. propose ice-free cryopreservation as a solution to these long-standing issues.
Heart valves were preserved by standard frozen cryopreservation (FC) or ice-free cryopreservation (IFC), thawed using standard protocols, and implanted in a sheep model. One year after implantation, the inflammatory and structural properties of the valves were assessed. While signs of inflammation were present in half of the FC valves, the IFC valves were free of immune cell infiltration. Further, the structural integrity of IFC valves more closely mirrored untransplanted valves.
Altogether, these data suggest that IFC may improve the current practice of heart valve replacement. It would allow valves to be stored at -80°C while potentially increasing longevity in the recipient. As one of the six sheep recieving an IFC valve was excluded from the study due to a heart valve infection and some of the FC and IFC valve structural measures were not significantly different, larger follow up studies could ensure that infections are not more common with IFC valves and could unequivocally determine the effect of preservation on heart valve structure. - Dr. Alyssa Ward
Jump to: OPA updates or Selected publications
Help keep the community updated by sending your news to alyssa.ward@organpreservationalliance.org
The Organ Donation Alliance is hosting the annual National Critical Issue Forum on enhancing organ utilization and transplantation. This year’s focus is on innovation - actionable technologies and systems that could overcome barriers to transplantation and improve logistics. Click here for more information and to register!
Dr. Kelvin Brockbank contributed to the paper highlighted above examining the long-term effects of implanting ice-free cryopreserved heart valves in sheep.
Dr. Kenneth Storey’s lab published popular science pieces in BioEssays and Science Trends and contriuted to efforts uncovering metabolic regulation modes in flies and analyzing the transcriptomes of hibernating marupials.
Dr. Ido Braslavsky investigated the atypical binding activity of an ice binding protein.
Dr. Barry Fuller reviewed cryopreservation in reproductive medicine.
Dr. Korkut Uygun’s and Dr. Gerald Brandacher’s labs collaborated to review machine perfusion in the context of vascular composite allograft preservation.
Dr. Boris Rubinsky and Dr. Michael Taylor’s labs showed that constant volume vitrication can be achieved at lower cryoprotectant concentrations than constant pressure protocols and that these constant volume chambers promote vitrification.
Dr. Mehmet Toner looked at how synthetic antifreeze compounds affect freezing temperatures.
Dr. Martin Mangino used an agent that has been shown to reduce ischemic injury to improve cardiopulminary resuscitation in a rat model.
Would you like to be involved with Biopreservation Briefings? Want your news included? E-mail alyssa.ward@organpreservationalliance.org with questions, ideas, and updates!
