scholarly journals Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes

2021 ◽  
Vol 12 ◽  
Author(s):  
Gaelen K. Dwyer ◽  
Hēth R. Turnquist
Keyword(s):  
Organ Transplantation ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Experimental Studies ◽  
Surgical Trauma ◽  
Solid Organ ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Detrimental inflammatory responses after solid organ transplantation are initiated when immune cells sense pathogen-associated molecular patterns (PAMPs) and certain damage-associated molecular patterns (DAMPs) released or exposed during transplant-associated processes, such as ischemia/reperfusion injury (IRI), surgical trauma, and recipient conditioning. These inflammatory responses initiate and propagate anti-alloantigen (AlloAg) responses and targeting DAMPs and PAMPs, or the signaling cascades they activate, reduce alloimmunity, and contribute to improved outcomes after allogeneic solid organ transplantation in experimental studies. However, DAMPs have also been implicated in initiating essential anti-inflammatory and reparative functions of specific immune cells, particularly Treg and macrophages. Interestingly, DAMP signaling is also involved in local and systemic homeostasis. Herein, we describe the emerging literature defining how poor outcomes after transplantation may result, not from just an over-abundance of DAMP-driven inflammation, but instead an inadequate presence of a subset of DAMPs or related molecules needed to repair tissue successfully or re-establish tissue homeostasis. Adverse outcomes may also arise when these homeostatic or reparative signals become dysregulated or hijacked by alloreactive immune cells in transplant niches. A complete understanding of the critical pathways controlling tissue repair and homeostasis, and how alloimmune responses or transplant-related processes disrupt these will lead to new immunotherapeutics that can prevent or reverse the tissue pathology leading to lost grafts due to chronic rejection.

scholarly journals Tryptophan Metabolism via Kynurenine Pathway: Role in Solid Organ Transplantation

2021 ◽  
Vol 22 (4) ◽  
pp. 1921
Author(s):  
Ruta Zulpaite ◽  
Povilas Miknevicius ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Immune Regulation ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Experimental Studies ◽  
Disease Patient ◽  
Kynurenine Pathway ◽  
Current Evidence ◽  
Solid Organ

Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during the last couple of decades; however, the field of transplantation still encounters several unique challenges, such as a shortage of transplantable organs and increasing pool of extended criteria donor (ECD) organs, which are extremely prone to ischemia-reperfusion injury (IRI), risk of graft rejection and challenges in immune regulation. Moreover, accurate and specific biomarkers, which can timely predict allograft dysfunction and/or rejection, are lacking. The essential amino acid tryptophan and, especially, its metabolites via the kynurenine pathway has been widely studied as a contributor and a therapeutic target in various diseases, such as neuropsychiatric, autoimmune disorders, allergies, infections and malignancies. The tryptophan-kynurenine pathway has also gained interest in solid organ transplantation and a variety of experimental studies investigating its role both in IRI and immune regulation after allograft implantation was first published. In this review, the current evidence regarding the role of tryptophan and its metabolites in solid organ transplantation is presented, giving insights into molecular mechanisms and into therapeutic and diagnostic/prognostic possibilities.

scholarly journals TLR2 and TLR4 in Ischemia Reperfusion Injury

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
F. Arslan ◽  
B. Keogh ◽  
P. McGuirk ◽  
A. E. Parker
Keyword(s):  
Myocardial Infarction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Innate Immune ◽  
Solid Organ ◽  
Beneficial Effects ◽  
Current State ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Ischemia reperfusion (I/R) injury refers to the tissue damage which occurs when blood supply returns to tissue after a period of ischemia and is associated with trauma, stroke, myocardial infarction, and solid organ transplantation. Although the cause of this injury is multifactorial, increasing experimental evidence suggests an important role for the innate immune system in initiating the inflammatory cascade leading to detrimental/deleterious changes. The Toll-like Receptors (TLRs) play a central role in innate immunity recognising both pathogen- and damage-associated molecular patterns and have been implicated in a range of inflammatory and autoimmune diseases. In this paper, we summarise the current state of knowledge linking TLR2 and TLR4 to I/R injury, including recent studies which demonstrate that therapeutic inhibition of TLR2 has beneficial effects on I/R injury in a murine model of myocardial infarction.

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 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 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 Impact of Melatonin in Solid Organ Transplantation—Is It Time for Clinical Trials? A Comprehensive Review

2018 ◽  
Vol 19 (11) ◽  
pp. 3509 ◽  
Author(s):  
Philipp Stiegler ◽  
Augustinas Bausys ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Peter Schemmer
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Experimental Studies ◽  
Organ Shortage ◽  
Solid Organ ◽  
Comprehensive Overview ◽  
Donor Pool ◽  
End Stage ◽  
New Strategies ◽  
Significant Mortality

Solid organ transplantation is the “gold standard” for patients with end-stage organ disease. However, the supply of donor organs is critical, with an increased organ shortage over the last few years resulting in a significant mortality of patients on waiting lists. New strategies to overcome the shortage of organs are urgently needed. Some experimental studies focus on melatonin to improve the donor pool and to protect the graft; however, current research has not reached the clinical level. Therefore, this review provides a comprehensive overview of the data available, indicating that clinical evaluation is warranted.

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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