scholarly journals Hemoglobin-Based Oxygen Carriers: Potential Applications in Solid Organ Preservation

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Cao ◽  
Guoqing Wang ◽  
Hongli He ◽  
Ruiming Yue ◽  
Yong Zhao ◽  
...  
Keyword(s):  
Organ Preservation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxygen Demand ◽  
Blood Substitutes ◽  
Solid Organ ◽  
Oxygen Carriers ◽  
Donor Pool ◽  
Potential Applications ◽  
Graft Quality

Ameliorating graft injury induced by ischemia and hypoxia, expanding the donor pool, and improving graft quality and recipient prognosis are still goals pursued by the transplant community. The preservation of organs during this process from donor to recipient is critical to the prognosis of both the graft and the recipient. At present, static cold storage, which is most widely used in clinical practice, not only reduces cell metabolism and oxygen demand through low temperature but also prevents cell edema and resists apoptosis through the application of traditional preservation solutions, but these do not improve hypoxia and increase oxygenation of the donor organ. In recent years, improving the ischemia and hypoxia of grafts during preservation and repairing the quality of marginal donor organs have been of great concern. Hemoglobin-based oxygen carriers (HBOCs) are “made of” natural hemoglobins that were originally developed as blood substitutes but have been extended to a variety of hypoxic clinical situations due to their ability to release oxygen. Compared with traditional preservation protocols, the addition of HBOCs to traditional preservation protocols provides more oxygen to organs to meet their energy metabolic needs, prolong preservation time, reduce ischemia–reperfusion injury to grafts, improve graft quality, and even increase the number of transplantable donors. The focus of the present study was to review the potential applications of HBOCs in solid organ preservation and provide new approaches to understanding the mechanism of the promising strategies for organ preservation.

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 Potential Applications of Extracellular Vesicles in Solid Organ Transplantation

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 369 ◽  
Author(s):  
Grange ◽  
Bellucci ◽  
Bussolati ◽  
Ranghino
Keyword(s):  
Extracellular Vesicles ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Solid Organ Transplantation ◽  
Cell Communication ◽  
Target Cells ◽  
Solid Organ ◽  
Term Survival ◽  
Potential Applications

Extracellular vesicles (EVs) play an important role in cell-to-cell communication by delivering coding and non-coding RNA species and proteins to target cells. Recently, the therapeutic potential of EVs has been shown to extend to the field of solid organ transplantations. Mesenchymal stromal cell-derived EVs (MSC-EVs) in particular have been proposed as a new tool to improve graft survival, thanks to the modulation of tolerance toward the graft, and to their anti-fibrotic and pro-angiogenic effects. Moreover, MSC-EVs may reduce ischemia reperfusion injury, improving the recovery from acute damage. In addition, EVs currently considered helpful tools for preserving donor organs when administered before transplant in the context of hypothermic or normothermic perfusion machines. The addition of EVs to the perfusion solution, recently proposed for kidney, lung, and liver grafts, resulted in the amelioration of donor organ viability and functionality. EVs may therefore be of therapeutic interest in different aspects of the transplantation process for increasing the number of available organs and improving their long-term survival.

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.

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 Dual and Opposite Costimulatory Targeting with a Novel Human Fusion Recombinant Protein Effectively Prevents Renal Warm Ischemia Reperfusion Injury and Allograft Rejection in Murine Models

2021 ◽  
Vol 22 (3) ◽  
pp. 1216
Author(s):  
Jordi Guiteras ◽  
Laura De Ramon ◽  
Elena Crespo ◽  
Nuria Bolaños ◽  
Silvia Barcelo-Batllori ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Recombinant Protein ◽  
Reperfusion Injury ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Solid Organ ◽  
Inflammatory Models

Many studies have shown both the CD28—D80/86 costimulatory pathway and the PD-1—PD-L1/L2 coinhibitory pathway to be important signals in modulating or decreasing the inflammatory profile in ischemia-reperfusion injury (IRI) or in a solid organ transplant setting. The importance of these two opposing pathways and their potential synergistic effect led our group to design a human fusion recombinant protein with CTLA4 and PD-L2 domains named HYBRI. The objective of our study was to determine the HYBRI binding to the postulated ligands of CTLA4 (CD80) and PD-L2 (PD-1) using the Surface Plasmon Resonance technique and to evaluate the in vivo HYBRI effects on two representative kidney inflammatory models—rat renal IRI and allogeneic kidney transplant. The Surface Plasmon Resonance assay demonstrated the avidity and binding of HYBRI to its targets. HYBRI treatment in the models exerted a high functional and morphological improvement. HYBRI produced a significant amelioration of renal function on day one and two after bilateral warm ischemia and on days seven and nine after transplant, clearly prolonging the animal survival in a life-sustaining renal allograft model. In both models, a significant reduction in histological damage and CD3 and CD68 infiltrating cells was observed. HYBRI decreased the circulating inflammatory cytokines and enriched the FoxP3 peripheral circulating, apart from reducing renal inflammation. In conclusion, the dual and opposite costimulatory targeting with that novel protein offers a good microenvironment profile to protect the ischemic process in the kidney and to prevent the kidney rejection, increasing the animal’s chances of survival. HYBRI largely prevents the progression of inflammation in these rat models.

scholarly journals Effects of Custodiol-N, a novel organ preservation solution, on ischemia/reperfusion injury

2010 ◽  
Vol 139 (4) ◽  
pp. 1048-1056 ◽  
Author(s):  
Sivakkanan Loganathan ◽  
Tamás Radovits ◽  
Kristóf Hirschberg ◽  
Sevil Korkmaz ◽  
Achim Koch ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Organ Preservation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Preservation Solution ◽  
Organ Preservation Solution

When does the lung die?K fc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung

1997 ◽  
Vol 83 (1) ◽  
pp. 247-252 ◽  
Author(s):  
David R. Jones ◽  
Randy M. Becker ◽  
Steve C. Hoffmann ◽  
John J. Lemasters ◽  
Thomas M. Egan
Keyword(s):  
Cell Viability ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Rat Lung ◽  
Donor Pool ◽  
Ischemic Time

Jones, David R., Randy M. Becker, Steve C. Hoffmann, John J. Lemasters, and Thomas M. Egan. When does the lung die? K fc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung. J. Appl. Physiol. 83(1): 247–252, 1997.—Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient ( K fc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. K fc increased with increasing postmortem ischemic time ( r = 0.88). Lungs ventilated with O2 1 h postmortem had similar K fc and wet-to-dry ratios as controls. Nonventilated lungs had threefold ( P < 0.05) and sevenfold ( P < 0.0001) increases in K fc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing K fc values ( r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal K fc with preharvest O2 ventilation. The relationship between K fc and TAN suggests that vascular permeability may be related to lung TAN levels.

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