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Hypothermic temperature effects on organ survival and restoration.

ABSTRACT: A three-dimensional multicellular organism maintains the biological functions of life support by using the blood circulation to transport oxygen and nutrients and to regulate body temperature for intracellular enzymatic reactions. Donor organ transplantation using low-temperature storage is used as the fundamental treatment for dysfunctional organs. However, this approach has a serious problem in that donor organs maintain healthy conditions only during short-term storage. In this study, we developed a novel liver perfusion culture system based on biological metabolism that can maintain physiological functions, including albumin synthesis, bile secretion and urea production. This system also allows for the resurrection of a severely ischaemic liver. This study represents a significant advance for the development of an ex vivo organ perfusion system based on biological metabolism. It can be used not only to address donor organ shortages but also as the basis of future regenerative organ replacement therapy.

SUBMITTER: Ishikawa J

PROVIDER: S-EPMC4405701 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Hypothermic temperature effects on organ survival and restoration.

Ishikawa Jun J Oshima Masamitsu M Iwasaki Fumitaka F Suzuki Ryoji R Park Joonhong J Nakao Kazuhisa K Matsuzawa-Adachi Yuki Y Mizutsuki Taro T Kobayashi Ayaka A Abe Yuta Y Kobayashi Eiji E Tezuka Katsunari K Tsuji Takashi T

Scientific reports 20150422

A three-dimensional multicellular organism maintains the biological functions of life support by using the blood circulation to transport oxygen and nutrients and to regulate body temperature for intracellular enzymatic reactions. Donor organ transplantation using low-temperature storage is used as the fundamental treatment for dysfunctional organs. However, this approach has a serious problem in that donor organs maintain healthy conditions only during short-term storage. In this study, we deve ...[more]

PMID: 25900715

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Project description:Resolution agonists, including lipid mediators and peptides such as annexin A1 (ANXA1), are providing novel approaches to treat inflammatory conditions. Surgical trauma exerts a significant burden on the immune system that can affect and impair multiple organs. Perioperative cerebral injury after cardiac surgery is associated with significant adverse neurological outcomes such as delirium and postoperative cognitive dysfunction. Using a clinically relevant rat model of cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA), we tested the pro-resolving effects of a novel bioactive ANXA1 tripeptide (ANXA1sp) on neuroinflammation and cognition. Male rats underwent 2?h CPB with 1?h DHCA at 18°C, and received vehicle or ANXA1sp followed by timed reperfusion up to postoperative day 7. Immortalized murine microglial cell line BV2 were treated with vehicle or ANXA1sp and subjected to 2?h oxygen-glucose deprivation followed by timed reoxygenation. Microglial activation, cell death, neuroinflammation, and NF-?B activation were assessed in tissue samples and cell cultures. Rats exposed to CPB and DHCA had evident neuroinflammation in various brain areas. However, in ANXA1sp-treated rats, microglial activation and cell death (apoptosis and necrosis) were reduced at 24?h and 7?days after surgery. This was associated with a reduction in key pro-inflammatory cytokines due to inhibition of NF-?B activation in the brain and systemically. Treated rats also had improved neurologic scores and shorter latency in the Morris water maze. In BV2 cells treated with ANXA1sp, similar protective effects were observed including decreased pro-inflammatory cytokines and cell death. Notably, we also found increased expression of ANXA1, which binds to NF-?B p65 and thereby inhibits its transcriptional activity. Our findings provide evidence that treatment with a novel pro-resolving ANXA1 tripeptide is neuroprotective after cardiac surgery in rats by attenuating neuroinflammation and may prevent postoperative neurologic complications.

Project description:Grassland restoration is gaining momentum worldwide to tackle the loss of biodiversity and associated ecosystem services. Restoration methods and their effects on ecological community reassembly have been extensively studied across various grassland types, while the importance of post-restoration management has so far received less attention. Grassland management is an important surrogate for natural disturbances, with which most ancient grasslands have coevolved. Thus, without the reintroduction of management-related disturbance, restoration targets are unlikely to be achieved in restored grasslands. In this study, we aimed to explore how 20 yr of management by mowing once a year or light cattle grazing affects restoration success in Palearctic meadow-steppe grasslands restored by either sowing native grasses (sown sites), applying Medicago sativa as a nurse plant (Medicago sites), or allowing spontaneous succession (spontaneous sites). We found that, following mowing, sown sites maintained long-lasting establishment limitation, while Medicago sites experienced a delay in succession. These limitations resulted in low total and target species richness, low functional redundancy, and distinct species and functional composition compared to reference data from ancient grasslands. Spontaneous sites that were mowed reached a more advanced successional stage, although they did not reach reference levels regarding most vegetation descriptors. Sown and Medicago sites that were grazed had higher total and target species richness than those that were mowed, and showed restoration success similar to that of spontaneous sites, on which grazing had only moderate further positive effects. Grazed sites, irrespective of the restoration method, were uniformly species rich, functionally diverse, and functionally redundant, and thus became important biodiverse habitats with considerable resilience. We conclude that an optimally chosen post-restoration management may have an impact on long-term community reassembly comparable to the choice of restoration method. Restoration planners may, therefore, need to put more emphasis on future management than on the initial restoration method. However, our findings also imply that if local constraints, such as potentially high invasive propagule pressure, necessitate the application of restoration methods that could also hinder the establishment of target species, the long-term recovery of the grassland can still be ensured by wisely chosen post-restoration management.

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Hypothermic temperature effects on organ survival and restoration.

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Hypothermic temperature effects on organ survival and restoration.

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