Molecular strategies used by hibernators: Potential therapeutic directions for ischemia reperfusion injury and preservation of human donor organs

Soo, Elizabeth; Welch, Alexander; Marsh, Christopher L.; McKay, Dianne B.

doi:10.1016/j.trre.2019.100512

Cited by 6 publications

(2 citation statements)

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“…Apart from their natural resistance to muscle atrophy, hibernators are also able to preserve the functionality of their organs over the long-term while into a hypometabolic state notably through body protein sparing via inhibition of protein degradation (see above). They therefore constitute very good models for the improvement of the preservation of tissues and organs for transplantation (Ratigan and McKay, 2016 ; Soo et al, 2020 ) ( Figure 3 ). If interbout arousals during hibernation in small mammals have a lot to teach regarding notably ischemia–reperfusion injury problems in the context of the cold storage of organs (Zancanaro et al, 1999 ; Soo et al, 2020 ), the concept of normothermic or sub-normothermic organ preservation has gained much attention in recent years.…”

Section: Hibernators As Good Models To Study the Maintenance Of Musclmentioning

confidence: 99%

“…They therefore constitute very good models for the improvement of the preservation of tissues and organs for transplantation (Ratigan and McKay, 2016 ; Soo et al, 2020 ) ( Figure 3 ). If interbout arousals during hibernation in small mammals have a lot to teach regarding notably ischemia–reperfusion injury problems in the context of the cold storage of organs (Zancanaro et al, 1999 ; Soo et al, 2020 ), the concept of normothermic or sub-normothermic organ preservation has gained much attention in recent years. Not only normothermic organ conservation overcomes the main weaknesses of cold storage, e.g., by avoiding ischemia–reperfusion injury (Vogel et al, 2012 ), but it also allows much longer preservation times.…”

Section: Hibernators As Good Models To Study the Maintenance Of Musclmentioning

confidence: 99%

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Body Protein Sparing in Hibernators: A Source for Biomedical Innovation

et al. 2021

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Proteins are not only the major structural components of living cells but also ensure essential physiological functions within the organism. Any change in protein abundance and/or structure is at risk for the proper body functioning and/or survival of organisms. Death following starvation is attributed to a loss of about half of total body proteins, and body protein loss induced by muscle disuse is responsible for major metabolic disorders in immobilized patients, and sedentary or elderly people. Basic knowledge of the molecular and cellular mechanisms that control proteostasis is continuously growing. Yet, finding and developing efficient treatments to limit body/muscle protein loss in humans remain a medical challenge, physical exercise and nutritional programs managing to only partially compensate for it. This is notably a major challenge for the treatment of obesity, where therapies should promote fat loss while preserving body proteins. In this context, hibernating species preserve their lean body mass, including muscles, despite total physical inactivity and low energy consumption during torpor, a state of drastic reduction in metabolic rate associated with a more or less pronounced hypothermia. The present review introduces metabolic, physiological, and behavioral adaptations, e.g., energetics, body temperature, and nutrition, of the torpor or hibernation phenotype from small to large mammals. Hibernating strategies could be linked to allometry aspects, the need for periodic rewarming from torpor, and/or the ability of animals to fast for more or less time, thus determining the capacity of individuals to save proteins. Both fat- and food-storing hibernators rely mostly on their body fat reserves during the torpid state, while minimizing body protein utilization. A number of them may also replenish lost proteins during arousals by consuming food. The review takes stock of the physiological, molecular, and cellular mechanisms that promote body protein and muscle sparing during the inactive state of hibernation. Finally, the review outlines how the detailed understanding of these mechanisms at play in various hibernators is expected to provide innovative solutions to fight human muscle atrophy, to better help the management of obese patients, or to improve the ex vivo preservation of organs.

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Section: Hibernators As Good Models To Study the Maintenance Of Musclmentioning

confidence: 99%

Section: Hibernators As Good Models To Study the Maintenance Of Musclmentioning

confidence: 99%

Body Protein Sparing in Hibernators: A Source for Biomedical Innovation

et al. 2021

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Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability

Ludwig,

Abraham,

Schaaf

et al. 2024

American Journal of Transplantation

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Review of Current Machine Perfusion Therapeutics for Organ Preservation

Buchwald

Martins

2020

Transplantation

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Because of the high demand of organs, the usage of marginal grafts has increased. These marginal organs have a higher risk of developing ischemia-reperfusion injury, which can lead to posttransplant complications. Ex situ machine perfusion (MP), compared with the traditional static cold storage, may better protect these organs from ischemia-reperfusion injury. In addition, MP can also act as a platform for dynamic administration of pharmacological agents or gene therapy to further improve transplant outcomes. Numerous therapeutic agents have been studied under both hypothermic (1–8°C) and normothermic settings. Here, we review all the therapeutics used during MP in different organ systems (lung, liver, kidney, heart). The major categories of therapeutic agents include vasodilators, mesenchymal stem cells, antiinflammatory agents, antiinfection agents, siRNA, and defatting agents. Numerous animal and clinical studies have examined MP therapeutic agents, some of which have even led to the successful reconditioning of discarded grafts. More clinical studies, especially randomized controlled trials, will need to be conducted in the future to solidify these promising results and to define the role of MP therapeutic agents in solid organ transplantation.

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Molecular strategies used by hibernators: Potential therapeutic directions for ischemia reperfusion injury and preservation of human donor organs

Cited by 6 publications

References 100 publications

Body Protein Sparing in Hibernators: A Source for Biomedical Innovation

Body Protein Sparing in Hibernators: A Source for Biomedical Innovation

Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability

Review of Current Machine Perfusion Therapeutics for Organ Preservation

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