Topic Editors

Prof. Dr. Jerzy W. Kupiec-Weglinski
Department of Surgery, David Geffen School of Medicine at UCL, Los Angeles, CA 90095, USA
Prof. Dr. Joan Roselló-Catafau
Reperfusion Laboratory, Department of Experimental Pathology, Institut dÍnvestigacions Biomèdiques de Barcelona, Barcelona, Catalonia, Spain
Prof. Dr. René Adam
Centre Hépato-Biliaire, AP-PH, Hôpital Paul Brousse, 94800 Paris, France
Prof. Dr. Teresa Carbonell Camós
Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain
Dr. Arnau Panisello-Roselló
Experimental Pathology Department, Institute of Biomedical Research of Barcelona(IIBB), CSIC-IDIBAPS, 08036 Barcelona, Catalonia, Spain

Sterile Inflammation in Solid Organ Transplantation

Abstract submission deadline
15 August 2022
Manuscript submission deadline
15 October 2022
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3728

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
Prof. Dr. Teresa Carbonell Camós
Dr. Arnau Panisello-Roselló
Topic Editors

Keywords

  • sterile inflammation
  • ischemia and reperfusion injury in organ transplantation
  • inflammasomes
  • DAMPS
  • cytokines
  • nitric oxide
  • oxidative and endoplasmic reticulum stress
  • mitochondrial markers (complexes I, II, III, ALDH2, UCP, UCP2)
  • autophagy and cell death and apoptosis
  • ferropoptosis and necropoptosis
  • ischemia-reperfusion injury and organ transplantation (heart, liver, lung, pancreas, kidney, small intestine)
  • ischemia-reperfusion injury prevention and therapeutic strategies (preconditioning and post conditioning)
  • adaptative and innate immunity responses
  • graft static preservation and machine perfusion (hypothermic and normothermic and markers: Krebs cycle, mitochondrial markers, AMP kinases, glycocalyx)
  • antioxidants and therapeutic strategies

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
International Journal of Molecular Sciences
ijms
6.208 6.9 2000 16.1 Days 2300 CHF Submit
Biomedicines
biomedicines
4.757 3.0 2013 17.2 Days 2200 CHF Submit
Antioxidants
antioxidants
7.675 6.5 2012 16.5 Days 2200 CHF Submit
Current Issues in Molecular Biology
cimb
2.976 2.7 1999 16.3 Days 1800 CHF Submit
Journal of Clinical Medicine
jcm
4.964 4.4 2012 20.4 Days 2400 CHF Submit

Published Papers (4 papers)

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Review
Liver Graft Hypothermic Static and Oxygenated Perfusion (HOPE) Strategies: A Mitochondrial Crossroads
Int. J. Mol. Sci. 2022, 23(10), 5742; https://doi.org/10.3390/ijms23105742 - 20 May 2022
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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Article
Intermittent Exposure of Hypercapnia Suppresses Allograft Rejection via Induction of Treg Differentiation and Inhibition of Neutrophil Accumulation
Biomedicines 2022, 10(4), 836; https://doi.org/10.3390/biomedicines10040836 - 01 Apr 2022
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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Review
Necroptosis in Solid Organ Transplantation: A Literature Overview
Int. J. Mol. Sci. 2022, 23(7), 3677; https://doi.org/10.3390/ijms23073677 - 27 Mar 2022
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)
Article
Immature Testicular Tissue Engineered from Weaned Mice to Adults for Prepubertal Fertility Preservation—An In Vivo Translational Study
Int. J. Mol. Sci. 2022, 23(4), 2042; https://doi.org/10.3390/ijms23042042 - 12 Feb 2022
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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