February 2018
A special thanks to this month's contributors: Dr. Peter Kilbride, Dr. Krishnaa Mahbubani, Dr. Bradley Weegman, Dr. Alireza Abazari Dr. Eugene Sato, and Dr. Kate Franz
Edited by Dr. Alyssa Ward and Jedd Lewis
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, News from our network, or Funding opportunities
We would like to express our heartfelt gratitude to our founder, Dr. Sebastian Giwa, who left his remaining leadership position at OPA (Chairman of the Board of Directors) at the close of 2017. Seb, of course, maintains his commitment to this grand challenge we’ve embarked on solving and has stepped back from OPA only to increase his hands-on attention to his other projects in organ banking and transforming human health.
Read Seb’s goodbye letter here.
The Pineapple Fund has generously donated $2 million to the Organ Preservation Alliance to kickstart programs directly supporting organ and tissue preservation research. This donation will largely be used as a matching commitment to establish at least one large organ banking research center, with initial seed funding of $5-10 million from OPA’s philanthropic community and institutional matching. We are seeking wide input from the community on where the center should be headquartered, how to structure it, and what the research focus should be.
See the funding section below for more details, or to submit an informal proposal to establish an organ banking research center at your institution!
Thanks largely to a matching commitment created by Ossium’s three co-founders (OPA’s founder Dr. Sebastian Giwa, OPA advisor Dr. Erik Woods, and OPA co-founder and board member Kevin Caldwell), OPA’s core advocacy programs grew tremendously in 2017. Now they have pledged to match the first $250,000 raised for OPA’s advocacy programs in 2018.
Last year’s funding has made many efforts possible that are now pushing this effort forward, from the second global Organ Banking Summit to the publication of a high-profile consensus article in Nature Biotechnology, to successful partnerships with major stakeholder organizations like AST, ASME, and CNTRP, to the launch of multiple technology roadmapping projects.
We are excited to continue this work in 2018, with help from Ossium and the rest of the community. Please consider donating (organpreservationalliance.org/donate) and/or flagging the matching challenge for friends who may want make a tax-deductible contribution to advance human health.
Feel free to email jedd@organpreservationalliance.org to discuss ways to help us meet this matching goal.
Jump to: OPA updates, News from our network, or Funding opportunities
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!
Despite the dire need for hearts to save patients with end-stage heart failure and heart disease, only ~30% of hearts from eligible organ donors are actually transplanted in the U.S. (Colvin et al. 2017). The currently short preservation times for thoracic organs fuels this discard of organs that could otherwise be used.
Wan et al. sought to demonstrate the feasibility of preserving rodent hearts in a constant volume chamber at high subzero temperatures (Wan et al. 2018). This approach requires careful balance to exploit the lower solute concentrations during freezing while protecting the organ from the deleterious effects of high pressure. Indeed, the rodent organs stored at -4°C (under moderate pressure) were of comparable viability to those stored at 0°C (at atmospheric pressure) and there was significant injury at the lowest temperatures (under the highest pressures).
The damage at higher pressures is not worrying because one of the key benefits of this preservation technique is that it introduces another variable that can be optimized – pressure. Through careful optimization of all the experimental parameters – cryoprotectant composition and concentration, temperature, and pressure – preservation at constant volume holds promise for enabling more transplants for patients in need.
As organ and tissue preservation has the potential to revolutionize transplantation, it’s sometimes easy to forget that the benefits for biomedical research can be equally powerful. This work by Wang et al. highlights the way that improvements in cryopreservation, like the advent of the Hypothermosol-FRS preservative, can improve methods in basic and translational research.
Murine kidneys were preserved at 4°C for up to 4 days and subjected to single cell transcriptome analysis (Wang et al. 2018). The profiles obtained from kidneys preserved for up to 3 days were comparable to those obtained from fresh samples. This finding offers the potential to significantly improve the logistics for these single cell transcriptome experiments. And because this preservative solution has been extensively studied and made commercially available, these results are likely to be transferable to other organ systems and experimental contexts.
Adherent cell lines are used ubiquitously in labs across the world. While most researchers freeze and thaw these lines, precious few have optimized these steps.
Bahari et al. utilized directional freezing, a technique used to preserve limbs in a rat model last year (Arav et al. 2017), to preserve cells adhered to a slide. The group successfully optimized cryoprotectant concentration and freezing rate to increase cell viability by about 60% over traditional cryopreservation techniques (Bahari et al. 2018).
Aside from the benefit of higher viabilities, optimizing and standardizing cell line preservation within and between labs could increase the reproducibility of experiments, as it is likely to prevent cellular changes that may influence experimental outcomes (Karimi-Busheri et al. 2013). Additionally, some notoriously hard to preserve adherent lines, like hepatocytes, could be improved by directional freezing protocols that don't require cells to adhere to a substrate in their fragile, post-thaw state.
This month, Ferhat et al. reported efforts to identify the immunological underpinnings of ischemia reperfusion injury (IRI; damage resulting from the cessation and return of flow to an organ). Identification of the pathway(s) leading to this injury could result in pharmaceuticals capable of preventing pathway activation – preventing IRI and improving organ quality.
In a mouse line lacking IL-33, Ferhat et al. saw decreased inflammation and injury 24 hours after cutting off kidney flow (Ferhat et al. 2018). Specifically, IL-33 was found to expand a subset of immune cells associated with tissue homeostasis, inflammation, and wound healing.
The story, however, is more complex than just an immune pathway gone awry. Last month, Cao et al. published a protective effect of IL-33 when administered to mice daily for 5 days prior to the induction of IRI. As in Ferhat et al, Cao et al found that IL-33 expanded the same subset of cells, however this group found a protective effect of these cells, even when transferred to an immunocompromised mouse prior to IRI (Cao et al. 2018).
While these findings appear to be at odds with one another, it is possible for both groups to be correct – that deletion of IL-33 is beneficial, and addition of extra IL-33 is protective. In fact, previous work has shown that the timing and duration of IL-33 dictates whether its effects will be protective or injurious (Stremska et al. 2017; Liang et al. 2017).
Jump to: OPA updates, Selected publications, or Funding opportunities
Help keep the community updated by sending your news to alyssa.ward@organpreservationalliance.org
Congratulations to OPA Advisors Drs. Jason Acker and Robert Ben, their startup company, PanTHERA CryoSolutions, was recently featured here for the successes and promise of ice recrystallization inhibitor technology!
BioFabUSA has launched a newsletter - create a portal login here to receive updates about project calls and regenerative medicine news!
OPA Advisor publications and patents:
Dr. Kelvin Brockbank was recently granted a patent for a cell preservation technique involving glycolipids
Dr. Utkan Demirci was granted a patent for a novel imaging system and published a review of liver regenerative medicine
Dr. Gerald Brandacher's work on a composite material for soft tissue healing was also granted a patent
Dr. Mehmet Toner published an optimized method for quickly vitrifying circulating tumor cells (CTCs) for later use and two papers (in PNAS and MCR) on different aspects of these CTCs (available here and here)
Dr. Bohdan Pomahac published a review on face transplantation
Dr. Kenneth Storey published on stress mechanisms in Gene, Fish Physiology and Biochemistry, Cryobiology
Dr. Janet Elliott expanded our knowledge of isobaric systems in this new paper
Dr. Boris Rubinsky published on electroporation and one of our featured articles - constant volume heart preservation
Dr. Dayong Gao published a method to remove the glycerol from cryopreserved blood
Dr. Ido Braslavsky optimized a protocol for preserving common adherent cell lines highlighted above
Jump to: OPA updates, Selected publications, or News from our network
From our existing network of philanthropic donors, OPA is raising $5-10 million in unrestricted funding during 2018-19 in order to launch one or more research centers dedicated to organ and tissue cryopreservation. We’re kicking this off with a $1 million matching commitment by OPA, made possible by the generosity of the Pineapple Fund (pineapplefund.org). Some of this funding can be released immediately for initial center infrastructure, including beginning to seek $10s of millions in government funding awards with OPA’s help.
Rather than simply writing a check and leaving you to fend for yourselves, OPA will act as a full partner in the research center’s growth and development. Employing a team of professional grantwriters and fundraisers and applying our own unique capabilities, we’ll help you with grantseeking and fundraising, partnership development, communications, recruiting, outreach, project management and administration. In other words, to a large extent we’ll keep the executive responsibilities off your plate and let the researchers focus on doing great research. For more on OPA’s track record at related activities, visit our media coverage page (organpreservationalliance.org/media/).
To learn more and to submit an informal proposal to establish a research center at your institution, click here for the request for proposals. Or email jedd@organpreservationalliance.org to learn more.
Would you like to be involved with Biopreservation Briefings? Want your news included? E-mail alyssa.ward@organpreservationalliance.org with questions, ideas, and updates!
