scholarly journals The Role of Metabolomics in Current Concepts of Organ Preservation

2020 ◽  
Vol 21 (18) ◽  
pp. 6607
Author(s):  
Mindaugas Kvietkauskas ◽  
Viktorija Zitkute ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Metabolic Profiling ◽  
Organ Preservation ◽  
Large Scale ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Supply And Demand ◽  
Solid Organ Transplantation ◽  
Special Focus ◽  
Solid Organ ◽  
Organ Quality

In solid organ transplantation (Tx), both survival rates and quality of life have improved dramatically over the last few decades. Each year, the number of people on the wait list continues to increase, widening the gap between organ supply and demand. Therefore, the use of extended criteria donor grafts is growing, despite higher susceptibility to ischemia-reperfusion injury (IRI) and consecutive inferior Tx outcomes. Thus, tools to characterize organ quality prior to Tx are crucial components for Tx success. Innovative techniques of metabolic profiling revealed key pathways and mechanisms involved in IRI occurring during organ preservation. Although large-scale trials are needed, metabolomics appears to be a promising tool to characterize potential biomarkers, for the assessment of graft quality before Tx and evaluate graft-related outcomes. In this comprehensive review, we summarize the currently available literature on the use of metabolomics in solid organ Tx, with a special focus on metabolic profiling during graft preservation to assess organ quality prior to Tx.

scholarly journals The Endothelial Glycocalyx and Organ Preservation—From Physiology to Possible Clinical Implications for Solid Organ Transplantation

2021 ◽  
Vol 22 (8) ◽  
pp. 4019
Author(s):  
Simon Mathis ◽  
Gabriel Putzer ◽  
Stefan Schneeberger ◽  
Judith Martini
Keyword(s):  
Organ Transplantation ◽  
Organ Preservation ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Endothelial Glycocalyx ◽  
Solid Organ ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

The endothelial glycocalyx is a thin layer consisting of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal side of vascular endothelial cells. It acts as a barrier and contributes to the maintenance of vascular homeostasis and microperfusion. During solid organ transplantation, the endothelial glycocalyx of the graft is damaged as part of Ischemia Reperfusion Injury (IRI), which is associated with impaired organ function. Although several substances are known to mitigate glycocalyx damage, it has not been possible to use these substances during graft storage on ice. Normothermic machine perfusion (NMP) emerges as an alternative technology for organ preservation and allows for organ evaluation, but also offers the possibility to treat and thus improve organ quality during storage. This review highlights the current knowledge on glycocalyx injury during organ transplantation, presents ways to protect the endothelial glycocalyx and discusses potential glycocalyx protection strategies during normothermic machine perfusion.

scholarly journals Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review

2020 ◽  
Vol 21 (2) ◽  
pp. 631 ◽  
Author(s):  
Lina Jakubauskiene ◽  
Matas Jakubauskas ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Positive Impact ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Comprehensive Review ◽  
Long Term Treatment

In recent decades, solid organ transplantation (SOT) has increased the survival and quality of life for patients with end-stage organ failure by providing a potentially long-term treatment option. Although the availability of organs for transplantation has increased throughout the years, the demand greatly outweighs the supply. One possible solution for this problem is to extend the potential donor pool by using extended criteria donors. However, organs from such donors are more prone to ischemia reperfusion injury (IRI) resulting in higher rates of delayed graft function, acute and chronic graft rejection and worse overall SOT outcomes. This can be overcome by further investigating donor preconditioning strategies, graft perfusion and storage and by finding novel therapeutic agents that could reduce IRI. relaxin (RLX) is a peptide hormone with antifibrotic, antioxidant, anti-inflammatory and cytoprotective properties. The main research until now focused on heart failure; however, several preclinical studies showed its potentials for reducing IRI in SOT. The aim of this comprehensive review is to overview currently available literature on the possible role of RLX in reducing IRI and its positive impact on SOT.

scholarly journals Immunomodulatory Properties of Mesenchymal Stromal Cells Can Vary in Genetically Modified Rats

2021 ◽  
Vol 22 (3) ◽  
pp. 1181
Author(s):  
Natalie Vallant ◽  
Bynvant Sandhu ◽  
Karim Hamaoui ◽  
Maria Prendecki ◽  
Charles Pusey ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Fluorescent Protein ◽  
Ischemia Reperfusion Injury ◽  
Genetically Modified ◽  
Ischemia Reperfusion ◽  
Expression Patterns ◽  
Solid Organ Transplantation ◽  
Solid Organ

Mesenchymal Stromal Cells (MSC) have been shown to exhibit immuno-modulatory and regenerative properties at sites of inflammation. In solid organ transplantation (SOT), administration of MSCs might lead to an alleviation of ischemia-reperfusion injury and a reduction of rejection episodes. Previous reports have suggested ‘MSC-preconditioning’ of macrophages to be partly responsible for the beneficial effects. Whether this results from direct cell-cell interactions (e.g., MSC trans-differentiation at sites of damage), or from paracrine mechanisms, remains unclear. Immunosuppressive capacities of MSCs from donors of different age and from genetically modified donor animals, often used for in-vivo experiments, have so far not been investigated. We conducted an in vitro study to compare paracrine effects of supernatants from MSCs extracted from young and old wild-type Wystar-Kyoto rats (WKY-wt), as well as young and old WKY donor rats positive for the expression of green fluorescent protein (WKY-GFP), on bone marrow derived macrophages (BMDM). Expression levels of Mannose receptor 1 (Mrc-1), Tumor necrosis factor α (TNFα), inducible NO synthase (iNos) and Interleukin-10 (IL-10) in BMDMs after treatment with different MSC supernatants were compared by performance of quantitative PCR. We observed different expression patterns of inflammatory markers within BMDMs, depending on age and genotype of origin for MSC supernatants. This must be taken into consideration for preclinical and clinical studies, for which MSCs will be used to treat transplant patients, aiming to mitigate inflammatory and allo-responses.

scholarly journals The Hepatoprotective Effect of Sodium Nitrite on Cold Ischemia-Reperfusion Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Li ◽  
Zihui Meng ◽  
Yuliang Liu ◽  
Rakesh P. Patel ◽  
John D. Lang
Keyword(s):  
Reperfusion Injury ◽  
Sodium Nitrite ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Solid Organ Transplantation ◽  
Liver Graft ◽  
Solid Organ ◽  
Post Transplantation ◽  
Cold Preservation

Liver ischemia-reperfusion injury is a major cause of primary graft non-function or initial function failure post-transplantation. In this study, we examined the effects of sodium nitrite supplementation on liver IRI in either Lactated Ringer's (LR) solution or University of Wisconsin (UW) solution. The syngeneic recipients of liver grafts were also treated with or without nitrite by intra-peritoneal injection. Liver AST and LDH release were significantly reduced in both nitrite-supplemented LR and UW preservation solutions compared to their controls. The protective effect of nitrite was more efficacious with longer cold preservation times. Liver histological examination demonstrated better preserved morphology and architecture with nitrite treatment. Hepatocellular apoptosis was significantly reduced in the nitrite-treated livers compared their controls. Moreover, liver grafts with extended cold preservation time of 12 to 24 hours demonstrated improved liver tissue histology and function post-reperfusion with either the nitrite-supplemented preservation solution or in nitrite-treated recipients. Interestingly, combined treatment of both the liver graft and recipient did not confer protection. Thus, nitrite treatment affords significant protection from cold ischemic and reperfusion injury to donor livers and improves liver graft acute function post-transplantation. The results from this study further support the potential for nitrite therapy to mitigate ischemia-reperfusion injury in solid organ transplantation.

scholarly journals Application of Mesenchymal Stem Cells During Machine Perfusion: An Emerging Novel Strategy for Organ Preservation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiale Li ◽  
Qinbao Peng ◽  
Ronghua Yang ◽  
Kunsheng Li ◽  
Peng Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Organ Transplantation ◽  
Organ Preservation ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Therapeutic Effects ◽  
Solid Organ ◽  
Machine Perfusion ◽  
Marginal Grafts

Although solid organ transplantation remains the definitive management for patients with end-stage organ failure, this ultimate treatment has been limited by the number of acceptable donor organs. Therefore, efforts have been made to expand the donor pool by utilizing marginal organs from donation after circulatory death or extended criteria donors. However, marginal organs are susceptible to ischemia-reperfusion injury (IRI) and entail higher requirements for organ preservation. Recently, machine perfusion has emerged as a novel preservation strategy for marginal grafts. This technique continually perfuses the organs to mimic the physiologic condition, allows the evaluation of pretransplant graft function, and more excitingly facilitates organ reconditioning during perfusion with pharmacological, gene, and stem cell therapy. As mesenchymal stem cells (MSCs) have anti-oxidative, immunomodulatory, and regenerative properties, mounting studies have demonstrated the therapeutic effects of MSCs on organ IRI and solid organ transplantation. Therefore, MSCs are promising candidates for organ reconditioning during machine perfusion. This review provides an overview of the application of MSCs combined with machine perfusion for lung, kidney, liver, and heart preservation and reconditioning. Promising preclinical results highlight the potential clinical translation of this innovative strategy to improve the quality of marginal grafts.

scholarly journals Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Pascal Rowart ◽  
Pauline Erpicum ◽  
Olivier Detry ◽  
Laurent Weekers ◽  
Céline Grégoire ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Critical Factor ◽  
Public Health Issue ◽  
Solid Organ ◽  
Short And Long Term

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT.

scholarly journals Hemoglobin-Based Oxygen Carriers: Potential Applications in Solid Organ Preservation

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Cao ◽  
Guoqing Wang ◽  
Hongli He ◽  
Ruiming Yue ◽  
Yong Zhao ◽  
...  
Keyword(s):  
Organ Preservation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxygen Demand ◽  
Blood Substitutes ◽  
Solid Organ ◽  
Oxygen Carriers ◽  
Donor Pool ◽  
Potential Applications ◽  
Graft Quality

Ameliorating graft injury induced by ischemia and hypoxia, expanding the donor pool, and improving graft quality and recipient prognosis are still goals pursued by the transplant community. The preservation of organs during this process from donor to recipient is critical to the prognosis of both the graft and the recipient. At present, static cold storage, which is most widely used in clinical practice, not only reduces cell metabolism and oxygen demand through low temperature but also prevents cell edema and resists apoptosis through the application of traditional preservation solutions, but these do not improve hypoxia and increase oxygenation of the donor organ. In recent years, improving the ischemia and hypoxia of grafts during preservation and repairing the quality of marginal donor organs have been of great concern. Hemoglobin-based oxygen carriers (HBOCs) are “made of” natural hemoglobins that were originally developed as blood substitutes but have been extended to a variety of hypoxic clinical situations due to their ability to release oxygen. Compared with traditional preservation protocols, the addition of HBOCs to traditional preservation protocols provides more oxygen to organs to meet their energy metabolic needs, prolong preservation time, reduce ischemia–reperfusion injury to grafts, improve graft quality, and even increase the number of transplantable donors. The focus of the present study was to review the potential applications of HBOCs in solid organ preservation and provide new approaches to understanding the mechanism of the promising strategies for organ preservation.

scholarly journals Current Status of Glucocorticoid Usage in Solid Organ Transplantation

2021 ◽  
Author(s):  
Simin Dashti-Khavidaki ◽  
Reza Saidi ◽  
Hong Lu
Keyword(s):  
Side Effects ◽  
Immunosuppressive Therapy ◽  
Organ Transplantation ◽  
Targeted Delivery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Current Status ◽  
Solid Organ ◽  
Advantages And Disadvantages

Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

Potential Roles of Siglecs in the Regulation of Allo-Immune Reaction

2019 ◽  
Vol 20 (8) ◽  
pp. 823-828 ◽  
Author(s):  
Songjie Cai ◽  
Jing Zhao ◽  
Takuya Ueno ◽  
Anil Chandraker
Keyword(s):  
Immune Reaction ◽  
Cell Function ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Innate Immune ◽  
Solid Organ ◽  
B Cell Tolerance ◽  
And Function

Siglecs are mammalian sialic acid (Sia) recognizing immuno-globulin-like receptors expressed across the major leukocyte lineages, and function to recognize ubiquitous Sia epitopes on the cell surface. Many Siglecs are inhibitory receptors expressed on innate immune cells, they also have a role in maintaining B cell tolerance as well as modulating the activation of conventional and plasmocytic dendritic cells. Through these and other roles they contribute directly and indirectly to the regulation of T cell function. Siglecs have been identified to play key roles in several forms of blood cancers, autoimmune and infection deceases. So far as we know, there’s no Siglecs related research works on solid organ transplantation. In this review, we describe our understanding of the potential roles of Siglecs in the regulation of immune cell function, which may be crosslinked to allo-rejection and ischemia-reperfusion injury.

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