Sterile Inflammation in Solid Organ Transplantation

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closed (15 August 2022)

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Topic Information

Dear Colleagues, 

Sterile inflammation (SI) has been associated with certain disease states, such as the increased tissue damage that results from ischemia associated with myocardial infarction, stroke and ischemia reperfusion (IRI) associated with organ transplantation (heart, lung, liver, pancreas, kidney and small intestine); also including the related adaptive and autoimmune responses. The life-saving benefits of organ transplantation can be thwarted by allograft dysfunction due to SI involved in the complex process of organ transplantation (organ recovery, graft preservation and machine perfusion strategies and then graft implant and revascularization) that limits the transplantation outcome, in which SI is contributing to ongoing cellular injury in transplanted organs (heart, lung, liver, pancreas, small intestine and kidney) leading to a “pleiade” of cell signalling cascades in graft transplant, with subsequent detrimental short- and long-term outcomes. Although the vicious cycle of sterile inflammation and cellular injury is remarkably consistent amongst different organs, the underlying mechanisms are poorly understood and need to be explored in depth to prevent the sterile inflammation associated with organ transplantation, including the recognition of antioxidant mechanisms and thus, mitigating IRI-induced graft damage to prevent attention being paid to allograft dysfunction. This Topic calls on the relevance of the sterile inflammation processes in IRI associated with organ transplantation and adaptive and innate immunity responses for establishing new protective strategies in clinical transplantation for the most suitable outcome and for rescuing sub-optimal organs to increase donor pool.

Prof. Dr. Jerzy W. Kupiec-Weglinski
Prof. Dr. Joan Roselló-Catafau
Prof. Dr. René Adam
Dr. Teresa Carbonell Camós
Dr. Arnau Panisello-Roselló
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900
Biomedicines biomedicines	3.9	5.2	2013	15.3 Days	CHF 2600
Antioxidants antioxidants	6.0	10.6	2012	15.5 Days	CHF 2900
Current Issues in Molecular Biology cimb	2.8	2.9	1999	16.8 Days	CHF 2200
Journal of Clinical Medicine jcm	3.0	5.7	2012	17.3 Days	CHF 2600

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Published Papers (6 papers)

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18 pages, 915 KiB  

Open AccessReview

Sterile Pancreas Inflammation during Preservation and after Transplantation

by Delphine Kervella, Benoît Mesnard, Thomas Prudhomme, Sarah Bruneau, Christophe Masset, Diego Cantarovich, Gilles Blancho and Julien Branchereau

Int. J. Mol. Sci. 2023, 24(5), 4636; https://doi.org/10.3390/ijms24054636 - 27 Feb 2023

Cited by 1 | Viewed by 2018

Abstract

The pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the [...] Read more.

The pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the pancreas linked to ischemia-reperfusion injury involves the activation of innate immune cell subsets such as macrophages and neutrophils, following tissue damage and release of damage-associated molecular patterns and pro-inflammatory cytokines. Macrophages and neutrophils favor tissue invasion by other immune cells, have deleterious effects or functions, and promote tissue fibrosis. However, some innate cell subsets may promote tissue repair. This outburst of sterile inflammation promotes adaptive immunity activation via antigen exposure and activation of antigen-presenting cells. Better controlling sterile inflammation during pancreas preservation and after transplantation is of utmost interest in order to decrease early allograft loss (in particular thrombosis) and increase long-term allograft survival. In this regard, perfusion techniques that are currently being implemented represent a promising tool to decrease global inflammation and modulate the immune response. Full article

(This article belongs to the Topic Sterile Inflammation in Solid Organ Transplantation)

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26 pages, 879 KiB  

Open AccessReview

Experimental and Clinical Aspects of Sevoflurane Preconditioning and Postconditioning to Alleviate Hepatic Ischemia-Reperfusion Injury: A Scoping Review

by Loïc Benoit, Audrey Dieu, Maxime Foguenne and Eliano Bonaccorsi-Riani

Int. J. Mol. Sci. 2023, 24(3), 2340; https://doi.org/10.3390/ijms24032340 - 25 Jan 2023

Cited by 8 | Viewed by 2005

Abstract

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the [...] Read more.

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI. Full article

(This article belongs to the Topic Sterile Inflammation in Solid Organ Transplantation)

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14 pages, 1141 KiB  

Open AccessReview

Liver Graft Hypothermic Static and Oxygenated Perfusion (HOPE) Strategies: A Mitochondrial Crossroads

by Raquel G. Bardallo, Rui T. Da Silva, Teresa Carbonell, Carlos Palmeira, Emma Folch-Puy, Joan Roselló-Catafau, René Adam and Arnau Panisello-Rosello

Int. J. Mol. Sci. 2022, 23(10), 5742; https://doi.org/10.3390/ijms23105742 - 20 May 2022

Cited by 7 | Viewed by 2849

Abstract

Marginal liver grafts, such as steatotic livers and those from cardiac death donors, are highly vulnerable to ischemia–reperfusion injury that occurs in the complex route of the graft from “harvest to revascularization”. Recently, several preservation methods have been developed to preserve liver grafts [...] Read more.

Marginal liver grafts, such as steatotic livers and those from cardiac death donors, are highly vulnerable to ischemia–reperfusion injury that occurs in the complex route of the graft from “harvest to revascularization”. Recently, several preservation methods have been developed to preserve liver grafts based on hypothermic static preservation and hypothermic oxygenated perfusion (HOPE) strategies, either combined or alone. However, their effects on mitochondrial functions and their relevance have not yet been fully investigated, especially if different preservation solutions/effluents are used. Ischemic liver graft damage is caused by oxygen deprivation conditions during cold storage that provoke alterations in mitochondrial integrity and function and energy metabolism breakdown. This review deals with the relevance of mitochondrial machinery in cold static preservation and how the mitochondrial respiration function through the accumulation of succinate at the end of cold ischemia is modulated by different preservation solutions such as IGL-2, HTK, and UW (gold-standard reference). IGL-2 increases mitochondrial integrity and function (ALDH2) when compared to UW and HTK. This mitochondrial protection by IGL-2 also extends to protective HOPE strategies when used as an effluent instead of Belzer MP. The transient oxygenation in HOPE sustains the mitochondrial machinery at basal levels and prevents, in part, the accumulation of energy metabolites such as succinate in contrast to those that occur in cold static preservation conditions. Additionally, several additives for combating oxygen deprivation and graft energy metabolism breakdown during hypothermic static preservation such as oxygen carriers, ozone, AMPK inducers, and mitochondrial UCP2 inhibitors, and whether they are or not to be combined with HOPE, are presented and discussed. Finally, we affirm that IGL-2 solution is suitable for protecting graft mitochondrial machinery and simplifying the complex logistics in clinical transplantation where traditional (static preservation) and innovative (HOPE) strategies may be combined. New mitochondrial markers are presented and discussed. The final goal is to take advantage of marginal livers to increase the pool of suitable organs and thereby shorten patient waiting lists at transplantation clinics. Full article

(This article belongs to the Topic Sterile Inflammation in Solid Organ Transplantation)

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14 pages, 2509 KiB  

Open AccessArticle

Intermittent Exposure of Hypercapnia Suppresses Allograft Rejection via Induction of Treg Differentiation and Inhibition of Neutrophil Accumulation

by Yuan-Sheng Tzeng, Yi-Jen Peng, Shih-En Tang, Kun-Lun Huang, Shi-Jye Chu, Shu-Yu Wu and Chia-Pi Cheng

Biomedicines 2022, 10(4), 836; https://doi.org/10.3390/biomedicines10040836 - 1 Apr 2022

Cited by 4 | Viewed by 2213

Abstract

Background: In the management of major burn wounds, allogeneic skin transplantation is a critical procedure to improve wound repair. Our previous works found that intermittent exposure to carbon dioxide leads to permissive hypercapnia (HCA) and prolongs skin allograft survival. However, the modulatory effects [...] Read more.

Background: In the management of major burn wounds, allogeneic skin transplantation is a critical procedure to improve wound repair. Our previous works found that intermittent exposure to carbon dioxide leads to permissive hypercapnia (HCA) and prolongs skin allograft survival. However, the modulatory effects of HCA exposure on the immune system are not well understood. Objectives: Our purpose was to investigate how intermittent exposure to HCA can effectively reduce the immune reaction to allogeneic skin graft rejection. Methods: A fully major histocompatibility complex-incompatible skin transplant from BALB/c to C57BL/6 mice model was utilized. Immune cells from splenic and draining lymph nodes were analyzed by flow cytometry. Serum proinflammatory cytokines were analyzed by ELISA. Results: Serum levels of IFN-γ, IL-2, IL-6, and TNF-α were significantly decreased in the HCA group. Additionally, the percentage of CD8+ cells in draining lymph nodes was significantly lower in HCA than in the control group. Moreover, the generation rate of FoxP3+ regulatory T cells (Tregs) from spleen naïve CD4+ T cells was increased by intermittent exposure to carbon dioxide. The infiltrated neutrophils were also eliminated by HCA. Taken together, we concluded that intermittent hypercapnia exposure could effectively suppress skin rejection by stimulating Treg cell generation and suppressing immune reactions. Full article

(This article belongs to the Topic Sterile Inflammation in Solid Organ Transplantation)

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13 pages, 292 KiB  

Open AccessReview

Necroptosis in Solid Organ Transplantation: A Literature Overview

by Beatrice Lukenaite, Erika Griciune, Bettina Leber, Kestutis Strupas, Philipp Stiegler and Peter Schemmer

Int. J. Mol. Sci. 2022, 23(7), 3677; https://doi.org/10.3390/ijms23073677 - 27 Mar 2022

Cited by 7 | Viewed by 2914

Abstract

Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition involving hypoxia, metabolic stress, leukocyte extravasation, cellular death (including apoptosis, necrosis and necroptosis) and an activation of immune response. Although the [...] Read more.

Ischemia-reperfusion injury (IRI) is encountered in various stages during solid organ transplantation (SOT). IRI is known to be a multifactorial inflammatory condition involving hypoxia, metabolic stress, leukocyte extravasation, cellular death (including apoptosis, necrosis and necroptosis) and an activation of immune response. Although the cycle of sterile inflammation during IRI is consistent among different organs, the underlying mechanisms are poorly understood. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be crucial in the implementation of necroptosis. Moreover, apart from “silent” apoptotic death, necrosis also causes sterile inflammation—necroinflammation, which is triggered by various damage-associated molecular patterns (DAMPs). Those DAMPs activate the innate immune system, causing local and systemic inflammatory responses, which can result in graft failure. In this overview we summarize knowledge on mechanisms of sterile inflammation processes during SOT with special focus on necroptosis and IRI and discuss protective strategies. Full article

(This article belongs to the Topic Sterile Inflammation in Solid Organ Transplantation)

14 pages, 3059 KiB  

Open AccessArticle

Immature Testicular Tissue Engineered from Weaned Mice to Adults for Prepubertal Fertility Preservation—An In Vivo Translational Study

by How Tseng, Yung-Liang Liu, Buo-Jia Lu and Chi-Huang Chen

Int. J. Mol. Sci. 2022, 23(4), 2042; https://doi.org/10.3390/ijms23042042 - 12 Feb 2022

Cited by 5 | Viewed by 2751

Abstract

Male pediatric survivors of cancers and bone marrow transplantation often require adjuvant chemoradiation therapy that may be gonadotoxic. The optimal methods to preserve fertility in these prepubertal males are still under investigation. This manuscript presents an in vivo experiment which involved transplantation of [...] Read more.

Male pediatric survivors of cancers and bone marrow transplantation often require adjuvant chemoradiation therapy that may be gonadotoxic. The optimal methods to preserve fertility in these prepubertal males are still under investigation. This manuscript presents an in vivo experiment which involved transplantation of immature testicular tissues (ITT) from transgenic donor, to wild-type recipient mice. Donors and recipients were age-mismatched (from 20-week-old donors to 3-week-old recipients, and vice versa) and the transplantation sites involved the abdomen, skin of the head, back muscle, and scrotum. The application of poly-l-lactic acid (PLLA) scaffold was also evaluated in age-matched donors and recipients (both 3-weeks-old). To quantitively evaluate the process of spermatogenesis after ITT transplantation and scaffold application, bioluminescence imaging (BLI) was employed. Our result showed that ITT from 3-week-old mice had the best potential for spermatogenesis, and the optimal transplantation site was in the scrotum. Spermatogenesis was observed in recipient mice up to 51 days after transplantation, and up to the 85th day if scaffold was used. The peak of spermatogenesis occurred between the 42nd and 55th days in the scaffold group. This animal model may serve as a framework for further studies in prepubertal male fertility preservation. Full article

(This article belongs to the Topic Sterile Inflammation in Solid Organ Transplantation)

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