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International Journal of Molecular... Apr 2023Liver transplantation is the only treatment for hepatic insufficiency as a result of acute and chronic liver injuries/pathologies that fail to recover. Unfortunately,... (Review)
Review
Liver transplantation is the only treatment for hepatic insufficiency as a result of acute and chronic liver injuries/pathologies that fail to recover. Unfortunately, there remains an enormous and growing gap between organ supply and demand. Although recipients on the liver transplantation waitlist have significantly higher mortality, livers are often not allocated because they are (i) classified as extended criteria or marginal livers and (ii) subjected to longer cold preservation time (>6 h) with a direct correlation of poor outcomes with longer cold ischemia. Downregulating the recipient's innate immune response to successfully tolerate a graft having longer cold ischemia times or ischemia-reperfusion injury through induction of immune tolerance in the graft and the host would significantly improve organ utilization and post-transplant outcomes. Broadly, technologies proposed for development aim to extend the life of the transplanted liver through post-transplant or recipient conditioning. In this review, we focus on the potential benefits of nanotechnology to provide unique pre-transplant grafting and recipient conditioning of extended criteria donor livers using immune tolerance induction and hyperthermic pre-conditioning.
Topics: Humans; Liver Transplantation; Liver; Tissue Donors; Reperfusion Injury; Liver Failure; Organ Preservation
PubMed: 37108659
DOI: 10.3390/ijms24087496 -
Molecular & Cellular Proteomics : MCP Jul 2014Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing...
Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing biological insight, informing drug and diagnostic development, and guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact of ischemia, we collected human ovarian tumor and breast cancer xenograft tissue without vascular interruption and performed quantitative proteomics and phosphoproteomics after defined ischemic intervals. Although the global expressed proteome and most of the >25,000 quantified phosphosites were unchanged after 60 min, rapid phosphorylation changes were observed in up to 24% of the phosphoproteome, representing activation of critical cancer pathways related to stress response, transcriptional regulation, and cell death. Both pan-tumor and tissue-specific changes were observed. The demonstrated impact of pre-analytical tissue ischemia on tumor biology mandates caution in interpreting stress-pathway activation in such samples and motivates reexamination of collection protocols for phosphoprotein analysis.
Topics: Animals; Breast Neoplasms; Cold Ischemia; Female; Gene Expression Profiling; Humans; Mice; Mice, Inbred NOD; Neoplasm Transplantation; Ovarian Neoplasms; Phosphoproteins; Phosphorylation; Proteome; Proteomics; Transplantation, Heterologous
PubMed: 24719451
DOI: 10.1074/mcp.M113.036392 -
New Biotechnology Sep 2019The accuracy of histopathological diagnosis is strictly reliant on adequate tissue preservation, which is completely dependent on pre-analytical variables. Among these... (Review)
Review
The accuracy of histopathological diagnosis is strictly reliant on adequate tissue preservation, which is completely dependent on pre-analytical variables. Among these variables, the time interval between the end of surgical excision to the onset of fixation (the cold ischemia time) may adversely affect preservation of tissue morphology, influencing the interpretation and reproducibility of diagnosis. During this time interval, the activation of enzymes may produce autolysis and degradation of antigens and nucleic acids, thus potentially affecting immunocytochemical and molecular results. Several studies have described under-vacuum at 4 °C storage of fresh surgical specimens as a safe and reliable method to control cold ischemia and preserve fresh tissues, as well as to standardize fixation times and implement tissue-banking. This review article gives a systematic overview of the advantages and drawbacks of the use of under-vacuum tissue preservation and cooling in surgical pathology, highlighting the impact this procedure may have on diagnostic and experimental pathology. It also documents our experience acquired within daily practice and national and international projects.
Topics: Cell Survival; Humans; Proteomics; Tissue Fixation; Tissue Preservation; Transcriptome; Vacuum
PubMed: 31150841
DOI: 10.1016/j.nbt.2019.05.007 -
Biopreservation and Biobanking Dec 2016Frequently investigators request that tissues be collected and processed in less than one hour following removal from a patient. Some biorepositories expend significant... (Review)
Review
Frequently investigators request that tissues be collected and processed in less than one hour following removal from a patient. Some biorepositories expend significant personnel time and other resources in trying to meet such goals; however, it is unclear whether the perceived benefits of relatively short cold ischemia times warrant these added costs. The literature of human surgical tissues prospectively exposed to cold ischemia at several time points was reviewed to compare the changes in transcripts/genes and microRNA with time of cold ischemia. Also, reports of protein changes in response to cold ischemia were correlated to changes in genes. The literature is limited; however, for most tissues, only a small proportion of transcripts/genes (<1%) changes up to 3 hours following surgery and most transcripts increase rather than decrease in less than 2 hours of cold ischemia. Biorepositories and investigators must consider the literature for evidence of significant changes in molecular results from tissues before spending significant resources on relatively rapid collection of tissues to meet cold ischemia times of less than 3 hours. Instead, those using human tissues in research must consider if the cold ischemia times affect their use in specific research; hence are these tissues "fit for purpose?"
Topics: Cold Ischemia; Gene Expression Regulation; Humans; MicroRNAs; RNA, Messenger; Time Factors; Tissue Preservation
PubMed: 27551929
DOI: 10.1089/bio.2016.0013 -
Clinical Journal of the American... Jun 2020Increased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia...
BACKGROUND AND OBJECTIVES
Increased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
The Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch).
RESULTS
Cold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ≥65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found.
CONCLUSIONS
We were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.
Topics: Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Cold Ischemia; Delayed Graft Function; Female; Humans; Infant; Infant, Newborn; Kidney Transplantation; Male; Middle Aged; Perfusion; Registries; Retrospective Studies; Risk Factors; Time Factors; Tissue Donors; United States; Young Adult
PubMed: 32404337
DOI: 10.2215/CJN.13711119 -
Clinical Journal of the American... Feb 2020
Topics: Allografts; Delayed Graft Function; Graft Survival; Humans; Kidney; Registries
PubMed: 31999257
DOI: 10.2215/CJN.14581119 -
Medicine Dec 2023The value of the crossmatch test in assessing pretransplant immunological risk is vital for clinical decisions, ranging from the indication of the transplant to the... (Review)
Review
The value of the crossmatch test in assessing pretransplant immunological risk is vital for clinical decisions, ranging from the indication of the transplant to the guidance of induction protocols and treatment with immunosuppressants. The crossmatch tests in transplantation can be physical or virtual, each with its advantages and limitations. Currently, the virtual crossmatch stands out for its sensitivity and specificity compared to the physical tests. Additionally, the virtual crossmatch can be performed in less time, allowing for a reduction in cold ischemia time. It shows a good correlation with the results of physical tests and does not negatively impact graft survival. Proper communication between clinicians and the transplant immunology laboratory will lead to a deeper understanding of each patient's immunological profile, better donor-recipient selection, and improved graft survival.
Topics: Humans; Graft Rejection; Graft Survival; Histocompatibility Testing; HLA Antigens; Kidney Transplantation
PubMed: 38115324
DOI: 10.1097/MD.0000000000036527 -
Acta Biochimica Polonica 2018Organ injury during ischemia is one of the clinical problems of today's transplantation. It occurs during warm ischemia time (WIT) when the blood flow is cut off and... (Review)
Review
Organ injury during ischemia is one of the clinical problems of today's transplantation. It occurs during warm ischemia time (WIT) when the blood flow is cut off and during cold ischemia when a graft is chilled in situ until the circulation is restored to the recipient organism. Fast cooling of the organ slows down metabolism and activates intracellular enzymes, which minimizes the effects of warm ischemia. Unfortunately, hypothermia also results in inhibition of ATP synthesis, cell swelling and intracellular acidity. That is why research is continually being conducted to develop new fluids for rinsing and storing organs, as well as to optimize the composition of those that are already in use, which will allow for longer and more effective graft storage and restoration of their optimal functions after transplantation. This article provides current information on rinsing and storage fluids available on the global market. It also discusses tips for the fluid modifications with hormones and micronutrients.
Topics: Humans; Organ Preservation Solutions; Organ Transplantation; Reperfusion Injury; Temperature
PubMed: 29352749
DOI: 10.18388/abp.2017_2312 -
Biomedicine & Pharmacotherapy =... Sep 2023With the growing shortage of organs, improvements in donor organ protection are needed to meet the increasing demands for transplantation. Here, the aim was to...
With the growing shortage of organs, improvements in donor organ protection are needed to meet the increasing demands for transplantation. Here, the aim was to investigate the protective effect of cinnamaldehyde against ischemia-reperfusion injury (IRI) in donor hearts exposed to prolonged cold ischemia. Donor hearts were harvested from rats pretreated with or without cinnamaldehyde, then subjected to 24 h of cold preservation and 1 h of ex vivo perfusion. Hemodynamic changes, myocardial inflammation, oxidative stress, and myocardial apoptosis were evaluated. The PI3K/AKT/mTOR pathway involved in the cardioprotective effects of cinnamaldehyde was explored through RNA sequencing and western blot analysis. Intriguingly, cinnamaldehyde pretreatment remarkably improved cardiac function through increasing coronary flow, left ventricular systolic pressure, +dp/dt, and -dp/dt, decreasing coronary vascular resistance and left ventricular end-diastolic pressure. Moreover, our findings indicated that cinnamaldehyde pretreatment protected the heart from IRI by alleviating myocardial inflammation, attenuating oxidative stress, and reducing myocardial apoptosis. Further studies showed that the PI3K/AKT/mTOR pathway was activated after cinnamaldehyde treatment during IRI. The protective effects of cinnamaldehyde were abolished by LY294002. In conclusion, cinnamaldehyde pretreatment alleviated IRI in donor hearts suffering from prolonged cold ischemia. Cinnamaldehyde exerted cardioprotective effects through the activation of the PI3K/AKT/mTOR pathway.
Topics: Rats; Animals; Humans; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Heart Transplantation; Rats, Sprague-Dawley; Myocardial Reperfusion Injury; Tissue Donors; TOR Serine-Threonine Kinases; Apoptosis; Inflammation
PubMed: 37385214
DOI: 10.1016/j.biopha.2023.114867 -
Journal of Clinical Medicine May 2019: Uterus transplantation (UTx) is a promising treatment for uterine infertility that has resulted in several births since 2014. Ischemia is a key step in organ... (Review)
Review
: Uterus transplantation (UTx) is a promising treatment for uterine infertility that has resulted in several births since 2014. Ischemia is a key step in organ transplantation because it may lead to changes jeopardizing graft viability. : We performed a systematic review of animal and human studies relating to uterine ischemia. : We retained 64 studies published since 2000. There were 35 studies in animals, 24 in humans, and five literature reviews. Modest preliminary results in large animals and humans are limited but encouraging. In small animals, pregnancies have been reported to occur after 24 h of cold ischemia (CI). In ewes, uterine contractions have been detected after 24 h of CI. Furthermore, it has been shown in animals that uterine tolerance to CI and to warm ischemia (WI) can be increased by pharmacological products. In women, mean CI time in studies of births from uteri obtained from live donors was between 2 h 47 min and 6 h 20 min from a deceased donor; with only one birth in this case. Muscle contractions have also been demonstrated in myometrial samples from women, after six or more hours of CI. : The uterus seems to be able to tolerate a prolonged period of CI, of at least six hours. Studies of the ischemia tolerance of the uterus and ways to improve it are essential for the development of UTx, particularly for procedures using grafts from deceased donors.
PubMed: 31146406
DOI: 10.3390/jcm8060760