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 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 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 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 Combination of mesenchymal stromal cells and machine perfusion is a novel strategy for organ preservation in solid organ transplantation

2021 ◽  
Author(s):  
Lingfei Zhao ◽  
Chenxia Hu ◽  
Fei Han ◽  
Dajin Chen ◽  
Yanhong Ma ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Organ Preservation ◽  
Ex Vivo ◽  
Solid Organ Transplantation ◽  
Organ Shortage ◽  
Solid Organ ◽  
Machine Perfusion ◽  
Organ Function

AbstractOrgan preservation is a prerequisite for an urgent increase in the availability of organs for solid organ transplantation (SOT). An increasing amount of expanded criteria donor (ECD) organs are used clinically. Currently, the paradigm of organ preservation is shifting from simple reduction of cellular metabolic activity to maximal simulation of an ex vivo physiological microenvironment. An ideal organ preservation technique should not only preserve isolated organs but also offer the possibility of rehabilitation and evaluation of organ function prior to transplantation. Based on the fact that mesenchymal stromal cells (MSCs) possess strong regeneration properties, the combination of MSCs with machine perfusion (MP) is expected to be superior to conventional preservation methods. In recent years, several studies have attempted to use this strategy for SOT showing promising outcomes. With better organ function during ex vivo preservation and the potential of utilization of organs previously deemed untransplantable, this strategy is meaningful for patients with organ failure to help overcome organ shortage in the field of SOT.

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.

scholarly journals Hyperspectral Imaging and Machine Perfusion in Solid Organ Transplantation: Clinical Potentials of Combining Two Novel Technologies

2021 ◽  
Vol 10 (17) ◽  
pp. 3838
Author(s):  
Margot Fodor ◽  
Julia Hofmann ◽  
Lukas Lanser ◽  
Giorgi Otarashvili ◽  
Marlene Pühringer ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Hyperspectral Imaging ◽  
Survival Rates ◽  
Solid Organ Transplantation ◽  
Organ Shortage ◽  
Solid Organ ◽  
Machine Perfusion ◽  
Novel Technologies ◽  
Normothermic Machine Perfusion ◽  
Reduction Of Mortality

Organ transplantation survival rates have continued to improve over the last decades, mostly due to reduction of mortality early after transplantation. The advancement of the field is facilitating a liberalization of the access to organ transplantation with more patients with higher risk profile being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of marginal donors. In this regard, hypothermic and normothermic machine perfusion are recognized as one of the most important developments in the modern era. Owing to these developments, novel non-invasive tools for the assessment of organ quality are on the horizon. Hyperspectral imaging represents a potentially suitable method capable of evaluating tissue morphology and organ perfusion prior to transplantation. Considering the changing environment, we here discuss the hypothetical combination of organ machine perfusion and hyperspectral imaging as a prospective feasibility concept in organ transplantation.

scholarly journals Hydrogen: Potential Applications in Solid Organ Transplantation

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Fuxun Yang ◽  
Yu Lei ◽  
Rongan Liu ◽  
Xiaoxiu Luo ◽  
Jiajia Li ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Clinical Studies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Organ Protection ◽  
Potential Applications

Ischemia reperfusion injury (IRI) in organ transplantation has always been an important hotspot in organ protection. Hydrogen, as an antioxidant, has been shown to have anti-inflammatory, antioxidant, and antiapoptotic effects. In this paper, the protective effect of hydrogen against IRI in organ transplantation has been reviewed to provide clues for future clinical studies.

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