Part 26 The world, from the past to the present, retold from the timelines.

Part 26

Article: Biotechnology My Blog Title: The world, from the past to the present, retold from the timelines.

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2023: [10.23] The first successful transplant of a functional cryopreserved mammalian kidney was reported. The study demonstrated a "nano-warming" technique for vitrification for up-to-100 days preservation of transplant organs. Sourced from [frontiersin.org] titled: “Supercooling: a promising technique for prolonged preservation in solid organ transplantation, and early perspectives in vascularized composite allografts.” METHODS: Literature on Pubmed and Google Scholar databases was reviewed by using the keywords and Boolean operators “Organ AND (Supercooling OR Subzero)”. The search was then repeated by replacing “Organ” with “Liver”, “Kidney”, “Heart”, “Lung”, “Skin”, “Adipo*”, “Bone”, “Nerve” and “VCA” successively. Additionally, reference lists were manually checked to identify other relevant articles. Non-original articles and articles in languages other than English and French were excluded. LITERATURE SCREENING RESULTS: The search strategy retrieved 339 total results. Title and abstract screening resulted in, including 45 results, covering liver, kidney, heart, lung, skin, fat/connective tissue, nerve, bone, and VCA ‘Vascularized Composite Allotransplantation’. Table 1 succinctly or briefly displayed the main results of the literature review, summarizing citations relevant to each organ and tissue supercooling. SUPERCOOLING PRINCIPLES TO EXTEND ORGAN PRESERVATION: Mitochondria play a critical role in the generation of metabolic energy in eukaryotic cells. They are responsible for most of the useful energy derived from the breakdown of carbohydrates and fatty acids, which is converted to adenosine triphosphate (ATP) by the process of oxidative phosphorylation. Oxidative phosphorylation (OXPHOS) consumes oxygen to produce ATP. For every cell in your body, the source of energy that keeps everything going is called ATP. Adenosine triphosphate (ATP) is the biochemical way to store and use energy. ATP is the most abundant energy-carrying molecule in your body. It harnesses the chemical energy found in food molecules and then releases it to fuel the work in the cell. ATP is a common currency for the cells in your body. The food you eat is digested into small subunits of macronutrients. The carbohydrates in your diet are all converted to a simple sugar (glucose). That first needs to be converted to ATP (the energy form that will work in the cell). Organ mitochondrial oxidative metabolism had been described to be reduced by half for every 10°C drop in temperature. Static cold storage (SCS) had utilized these principles for decades by storing organs at 4°C, mostly on ice. However, if this process allowed for decreasing ischemic injuries, storage at 4°C did not completely arrest cellular metabolism and limited the total preservation duration. Recent developments in machine-perfusion techniques had aimed to decrease these injuries by oxygenating the organ while being cooled: Hypothermic Oxygenated Machine Perfusion (HMP) had shown interesting results in liver and kidney transplantation. Sub-zero temperatures had the potential to further decrease cell metabolism. Intracellular ice formation was one of the main causes of cell death during sub-zero preservation. Ice formation was a stochastic phenomenon and increased in lower temperatures and larger tissue volumes. Freezing comprises two phenomena, namely ice nucleation, which consists of the random formation of ice crystals from the liquid, and solidification, which is the formation of ice due to growth of these nuclei. Ice nucleation is an activated process and therefore it is stochastic. Different approaches coexisted in these temperature ranges. Partial freezing consisted of using ice nucleators to control and limit ice formation and cryoprotective agents (CPAs) to maintain an unfrozen liquid phase. Cryoprotective agents (CPAs) are used to eliminate ice formation when cooling organs to cryogenic temperatures. Organs can be cryopreserved without ice formation if there is no limit to the amount of CPA that can be used, but toxicity of CPAs limits the amount that can be used. This preservation method allowed for storage at -10°C to -15°C and had shown positive outcomes in livers. Alternatively, Vitrification was a technique that involved rapidly cooling organs to achieve a stable, ice-free state with a glass-like consistency. However, the ice-nucleation issue arised when these organs were warmed back to normal temperatures. The formation of ice crystals had been a major limitation during vitrified organ recovery if the rewarming process was too slow. In addition, another risk was of cracking due to thermal stress if the rewarming was not done uniformly. Thermal stress is induced in a body when the temperature of the body is raised or lowered and the body is not allowed to expand or contract freely. Thermal stress includes both heat and cold stress.

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Picture sources: Peakpx.com and Pexels, Pixabay in PowerDirector and other websites:

1:https://i.ytimg.com/vi/RfA_7dUAEmE/maxresdefault.jpg

2:https://journals.sagepub.com/cms/10.1177/1357633X13512061/asset/b9e0b683-53d2-4335-b6ea-d9551e1e1640/assets/images/large/10.1177_1357633x13512061-fig3.jpg

3:https://upload.wikimedia.org/wikipedia/commons/c/c1/Google_Scholar_home_page.png

4:https://care.pressreader.com/hc/article_attachments/21642508467732

5:https://pbs.twimg.com/media/F0V4S36WcAEXoFQ?format=jpg&name=large

6:https://www.researchgate.net/figure/Phylogenetic-time-tree-of-mammalian-families-13-created-on-the-basis-of-an-analysis-of_fig1_51664364

7:https://www.researchgate.net/publication/381095877/figure/fig3/AS:11431281250106423@1717761276278/Perfusion-system-used-for-loading-and-recovery-and-detailed-supercooling-protocol-a.png

8:https://www.researchgate.net/publication/381095877/figure/fig2/AS:11431281250144033@1717761274630/Experimental-design-Four-hindlimbs-were-included-in-each-of-the-three-groups-undergoing.png

9:https://i0.wp.com/ncbiinsights.ncbi.nlm.nih.gov/wp-content/uploads/2022/03/Now-1920-%C3%97-1080-px-1.png?resize=1108%2C737&ssl=1