Supercooling preservation and transplantation of the rat liver

Bruinsma, Bote G.; Berendsen, Tim; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L.; Uygun, Korkut

doi:10.1038/nprot.2015.011

Cited by 60 publications

(39 citation statements)

References 30 publications

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“…Although leaps forward in machine perfusion 33–41,65–67 , organ cryopreservation 26,27,68 , understanding scientific mechanisms of ischemic injury and metabolic regulation 29–32,41 , and other areas have created a blueprint for transforming organ preservation, today maximum clinical organ preservation times are measured in hours, varying according to the organ transplanted, and necessitate transplantation almost immediately after the organ is recovered (http://www.nedonation.org/donation-guide/organ/acceptable-ischemic-times). Organs are rushed to their destinations, often by jet, or by helicopter flight straight to a landing pad on the transplant center rooftop.…”

Section: The Unrealized Potential Of Organ Transplantationmentioning

confidence: 99%

The promise of organ and tissue preservation to transform medicine

et al. 2017

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The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.

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Section: The Unrealized Potential Of Organ Transplantationmentioning

confidence: 99%

The promise of organ and tissue preservation to transform medicine

et al. 2017

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“…This has inspired researchers, notably Toner and Uygun’s group at Massachusetts General Hospital/Harvard, to apply knowledge of supercooling to develop a novel protocol enabling the viable preservation of rat livers at –6°C for 3–4 days [86, 109] (Fig. 2).…”

Section: High-subzero Preservationmentioning

confidence: 99%

“…This is significant, since 72 h (3 days) represents a more than 5- to 10-fold increase over current typical clinical practice. Berendsen et al [86] and Bruinsma et al [109] demonstrated that a simple first-generation supercooling protocol dramatically extends the preservation of rat livers. The method relies on several crucial components: (1) the use of subzero temperatures to slow metabolism during static storage while avoiding injury from freezing; (2) preservative agents (PEG and 3-OMG); and (3) a recovery step with subnormothermic machine perfusion, which mitigates cold ischemic injury.…”

Section: High-subzero Preservationmentioning

confidence: 99%

New Approaches to Cryopreservation of Cells, Tissues, and Organs

Taylor¹,

Weegman²,

Baicu³

et al. 2019

Transfus Med Hemother

120

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In this concept article, we outline a variety of new approaches that have been conceived to address some of the remaining challenges for developing improved methods of biopreservation. This recognizes a true renaissance and variety of complimentary, high-potential approaches leveraging inspiration by nature, nanotechnology, the thermodynamics of pressure, and several other key fields. Development of an organ and tissue supply chain that can meet the healthcare demands of the 21st century means overcoming twin challenges of (1) having enough of these lifesaving resources and (2) having the means to store and transport them for a variety of applications. Each has distinct but overlapping logistical limitations affecting transplantation, regenerative medicine, and drug discovery, with challenges shared among major areas of biomedicine including tissue engineering, trauma care, transfusion medicine, and biomedical research. There are several approaches to biopreservation, the optimum choice of which is dictated by the nature and complexity of the tissue and the required length of storage. Short-term hypothermic storage at temperatures a few degrees above the freezing point has provided the basis for nearly all methods of preserving tissues and solid organs that, to date, have proved refractory to cryopreservation techniques successfully developed for single-cell systems. In essence, these short-term techniques have been based on designing solutions for cellular protection against the effects of warm and cold ischemia and basically rely upon the protective effects of reduced temperatures brought about by Arrhenius kinetics of chemical reactions. However, further optimization of such preservation strategies is now seen to be restricted. Long-term preservation calls for much lower temperatures and requires the tissue to withstand the rigors of heat and mass transfer during protocols designed to optimize cooling and warming in the presence of cryoprotective agents. It is now accepted that with current methods of cryopreservation, uncontrolled ice formation in structured tissues and organs at subzero temperatures is the single most critical factor that severely restricts the extent to which tissues can survive procedures involving freezing and thawing. In recent years, this major problem has been effectively circumvented in some tissues by using ice-free cryopreservation techniques based upon vitrification. Nevertheless, despite these promising advances there remain several recognized hurdles to be overcome before deep-subzero cryopreservation, either by classic freezing and thawing or by vitrification, can provide the much-needed means for biobanking complex tissues and organs for extended periods of weeks, months, or even years. In many cases, the approaches outlined here, including new underexplored paradigms of high-subzero preservation, are novel and inspired by mechanisms of freeze tolerance, or freeze avoidance, in nature. Others apply new bioengineering techniques such as nanotechnology, isochoric pressure preserv...

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“…These in turn are raising exciting possibilities for organ conditioning or repair as novel therapies during the perfusion period, which may well become a “hot topic” for research over the next 10 years. The concept of true long-term organ preservation at deep sub-zero temperatures also seemed to be at an impasse in previous times [80], whereas now there are small signs of renewed interest and investigation [129, 159, 160], although these currently remain far from clinical application. In turn, they will depend on new kinds of dynamic perfusion.…”

Section: Summary and Future Horizonsmentioning

confidence: 99%

Organ Preservation into the 2020s: The Era of Dynamic Intervention

Petrenko

Carnevale

Somov

et al. 2019

Transfus Med Hemother

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Organ preservation has been of major importance ever since transplantation developed into a global clinical activity. The relatively simple procedures were developed on a basic comprehension of low-temperature biology as related to organs outside the body. In the past decade, there has been a significant increase in knowledge of the sequelae of effects in preserved organs, and how dynamic intervention by perfusion can be used to mitigate injury and improve the quality of the donated organs. The present review focuses on (1) new information about the cell and molecular events impacting on ischemia/reperfusion injury during organ preservation, (2) strategies which use varied compositions and additives in organ preservation solutions to deal with these, (3) clear definitions of the developing protocols for dynamic organ perfusion preservation, (4) information on how the choice of perfusion solutions can impact on desired attributes of dynamic organ perfusion, and (5) summary and future horizons.

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Supercooling preservation and transplantation of the rat liver

Cited by 60 publications

References 30 publications

The promise of organ and tissue preservation to transform medicine

The promise of organ and tissue preservation to transform medicine

New Approaches to Cryopreservation of Cells, Tissues, and Organs

Organ Preservation into the 2020s: The Era of Dynamic Intervention

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