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Recent Advancements in Organ Transplantation: From Organ Protection to Molecular...
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Recent Advancements in Organ Transplantation: From Organ Protection to Molecular Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4500

Special Issue Editors

Prof. Dr. Joan Roselló-Catafau

E-Mail Website
Guest Editor
Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Spain
Interests: organ (liver, pancreas, small intestine, kidney) transplantation; cell signaling molecular mechanisms in organ transplantation; graft therapeutics; preservation and preservation solutions
Special Issues, Collections and Topics in MDPI journals
Dr. Arnau Panisello-Roselló

E-Mail Website
Guest Editor
Experimental Pathology Department, Institut d’Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC)-IDIBAPS, CIBEREHD, 08036 Barcelona, Catalonia, Spain
Interests: liver transplantation; fatty liver; ubiquitin proteasome; liver; proteasome; liver diseases; transplantation; organ transplantation; organ donation
Special Issues, Collections and Topics in MDPI journals
Dr. Teresa Carbonell Camós

E-Mail Website
Guest Editor
Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain
Interests: oxidants and antioxidants in physiology; intermittent hypoxia and neuroprotection in postischemic processes; molecular mechanisms induced by hypothermia in isolated rat liver
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Organ transplantation (TX) is the best treatment for end-stage organ failure. However, the clinical needs outweigh the number of organs available, leading to significant and crucial organ shortage and forcing clinicians to use higher-risk organs for TX, such as Extended Criteria Donors (ECD), which are very vulnerable to ischemia-reperfusion injury (IRI) associated with TX.

IRI is the sum of damages accumulated during the complex TX process that originated from the deprivation of oxygen to the organ (in donor) and its subsequent restoration (in the recipient), including organ retrieval, static preservation, ex vivo dynamic perfusion and graft reperfusion. In all these steps, a “pleiade” of specific physiopathological mechanisms at a molecular level affects the organ's post-transplant function in the short and long term, which should be explored in depth.

This special IJMS issue draws attention to new static preservation and dynamic perfusion machine strategies (HOPE and NMP) to increase organ protection, based on new pharmacological treatments, including single-cell transcriptomics and mi-RNAs. Overall therapeutic targets would allow a better understanding of the underlying molecular pathophysiology mechanisms involved in clinical and experimental transplantation scenarios when marginal organs are specially used, such as steatotic livers.

Prof. Dr. Joan Roselló-Catafau
Dr. Arnau Panisello-Roselló
Dr. Teresa Carbonell Camós
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • organ (liver, pancreas, intestine, kidney) transplantation
  • ischemia-reperfusion injury
  • “ex vivo” static preservation and dynamic machine perfusion strategies
  • mitochondria
  • pharmacological treatments
  • mi-RNAs
  • redox-stress
  • inflammatory mediators
  • cell lines

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Published Papers (3 papers)

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Research

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16 pages, 1663 KiB  
Article
Assessing Biomarkers of Porcine Kidneys under Normothermic Machine Perfusion—Can We Gain Insight into a Marginal Organ?
by Carla Steinhauser, Abdulbaki Yakac, Wenke Markgraf, Susanne Kromnik, Andreas Döcke, Philipp Talhofer, Christine Thiele, Hagen Malberg, Ulrich Sommer, Gustavo B. Baretton, Susanne Füssel, Christian Thomas and Juliane Putz
Int. J. Mol. Sci. 2024, 25(19), 10280; https://doi.org/10.3390/ijms251910280 - 24 Sep 2024
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Abstract
To identify potentially transplantable organs in a pool of marginal kidneys, 33 porcine slaughterhouse kidneys were perfused for 4 h with whole blood. During the normothermic perfusion, plasma, urine, and tissue samples were taken. Several biomarkers for tubule injury, endothelial activation, and inflammatory [...] Read more.
To identify potentially transplantable organs in a pool of marginal kidneys, 33 porcine slaughterhouse kidneys were perfused for 4 h with whole blood. During the normothermic perfusion, plasma, urine, and tissue samples were taken. Several biomarkers for tubule injury, endothelial activation, and inflammatory response were evaluated for a potential correlation with macroscopic appearance, histology, and filtration activity. Generally, biomarker levels increased during perfusion. TLR-4, EDN-1, and NGAL were not associated with any classification. In contrast, a steeper increase in NAG and IL-6 in plasma correlated with a poor macroscopic appearance at 4 h, indicating a higher inflammatory response in the kidneys with worse macroscopy early on, potentially due to more damage at the tubules. Although long-term effects on the graft could not be assessed in this setting, early observation under machine perfusion with whole blood was feasible. It allowed the assessment of kidneys under conditions comparable to reperfusion. This setting could give surgeons further insight into the quality of marginal kidneys and an opportunity to pre-treat them. Full article
(This article belongs to the Special Issue Recent Advancements in Organ Transplantation: From Organ Protection to Molecular Therapy)
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13 pages, 2103 KiB  
Article
Ex Vivo Optimization of Donor Lungs with Inhaled Sevoflurane during Normothermic Ex Vivo Lung Perfusion (VITALISE): A Pilot and Feasibility Study in Sheep
by Timo Steinkühler, Shuqi Yang, Michiel A. Hu, Jayant S. Jainandunsing, Neeltina M. Jager, Michiel E. Erasmus, Michel M. R. F. Struys, Dirk J. Bosch, Matijs van Meurs, Matthieu Jabaudon, Damien Richard, Wim Timens, Henri G. D. Leuvenink and Gertrude J. Nieuwenhuijs-Moeke
Int. J. Mol. Sci. 2024, 25(4), 2413; https://doi.org/10.3390/ijms25042413 - 19 Feb 2024
Cited by 1 | Viewed by 1541
Abstract
Volatile anesthetics have been shown in different studies to reduce ischemia reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) facilitates graft evaluation, extends preservation time and potentially enables injury repair and improvement of lung quality. We hypothesized that ventilating lungs with sevoflurane during [...] Read more.
Volatile anesthetics have been shown in different studies to reduce ischemia reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) facilitates graft evaluation, extends preservation time and potentially enables injury repair and improvement of lung quality. We hypothesized that ventilating lungs with sevoflurane during EVLP would reduce lung injury and improve lung function. We performed a pilot study to test this hypothesis in a slaughterhouse sheep DCD model. Lungs were harvested, flushed and stored on ice for 3 h, after which EVLP was performed for 4 h. Lungs were ventilated with either an FiO2 of 0.4 (EVLP, n = 5) or FiO2 of 0.4 plus sevoflurane at a 2% end-tidal concentration (Cet) (S-EVLP, n = 5). Perfusate, tissue samples and functional measurements were collected and analyzed. A steady state of the target Cet sevoflurane was reached with measurable concentrations in perfusate. Lungs in the S-EVLP group showed significantly better dynamic lung compliance than those in the EVLP group (p = 0.003). Oxygenation capacity was not different in treated lungs for delta partial oxygen pressure (PO2; +3.8 (−4.9/11.1) vs. −11.7 (−12.0/−3.2) kPa, p = 0.151), but there was a trend of a better PO2/FiO2 ratio (p = 0.054). Perfusate ASAT levels in S-EVLP were significantly reduced compared to the control group (198.1 ± 93.66 vs. 223.9 ± 105.7 IU/L, p = 0.02). We conclude that ventilating lungs with sevoflurane during EVLP is feasible and could be useful to improve graft function. Full article
(This article belongs to the Special Issue Recent Advancements in Organ Transplantation: From Organ Protection to Molecular Therapy)
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Review

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19 pages, 2281 KiB  
Review
The Effect of Interleukin-10 Immunotherapy on Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis of Preclinical Studies
by Apostolos Prionas, Karim Hamaoui, Konstantinos Vanezis, Vikash Reebye, Nagy Habib and Vassilios Papalois
Int. J. Mol. Sci. 2024, 25(11), 6231; https://doi.org/10.3390/ijms25116231 - 5 Jun 2024
Cited by 1 | Viewed by 1559
Abstract
Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google [...] Read more.
Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: −9.177, −5.601, I2 = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: −11.000, −4.184, I2 = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1β, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: −8.917, −5.755, I2 = 22.71%), and long-term kidney fibrosis (95% CI: −6.963, −3.438, I2 = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials. Full article
(This article belongs to the Special Issue Recent Advancements in Organ Transplantation: From Organ Protection to Molecular Therapy)
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