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Transplant International : Official... 2023Organ preservation and assessment with machine perfusion (MP) has provided transplant physicians with the ability to evaluate and select grafts suitable for... (Review)
Review
Organ preservation and assessment with machine perfusion (MP) has provided transplant physicians with the ability to evaluate and select grafts suitable for transplantation. Nevertheless, the discard of organs considered too damaged still sustains the imbalance between donor organs supply and demands. Therefore, there is the pressing clinical need for strategies to repair and/or regenerate organs before transplantation, and MP is uniquely positioned to satisfy this need. The systemic administration of mesenchymal stromal cells (MSC) was shown to reduce ischemia-reperfusion injury in pre-clinical organ transplant models but could not be reproduced in clinical transplantation, largely because of inefficient cell delivery. The administration of MSC during MP is one strategy that recently gained much attention as an alternative delivery method to target MSC directly to the donor organ. However, careful reinterpretation of preliminary results reveals that this approach is equally limited by a suboptimal delivery of short-lived MSC to the target organ. In contrast, the use of MSC secretome and/or extracellular vesicles therapy during MP seems to be more efficient in harnessing MSC properties during MP. In this mini review we speculate on the future of the novel niche of organ repair and regeneration before transplantation.
Topics: Humans; Organ Preservation; Organ Transplantation; Regeneration; Perfusion; Mesenchymal Stem Cell Transplantation
PubMed: 38020754
DOI: 10.3389/ti.2023.11947 -
Journal of Orthopaedic Surgery and... Jun 2020Joints withstand huge forces, but little is known about subchondral pressures and perfusion during loading. We developed an in vitro calf foot model to explore...
BACKGROUND
Joints withstand huge forces, but little is known about subchondral pressures and perfusion during loading. We developed an in vitro calf foot model to explore intraosseous pressure (IOP) and subchondral perfusion during weight bearing.
METHODS
Freshly culled calf forefeet were perfused with serum. IOP was measured at three sites in the foot using intraosseous needles, pressure transducers, and digital recorders. IOP was measured during perfusion, with and without a tourniquet and with differing weights, including static loading and dynamic loading to resemble walking.
RESULTS
IOP varied with perfusion pressure. Static loading increased subchondral IOP whether the bone was non-perfused, perfused, or perfused with a proximal venous tourniquet (p < 0.0001). Under all perfusion states, IOP was proportional to the load (R = 0.984). Subchondral IOP often exceeded perfusion pressure. On removal of a load, IOP fell to below the pre-load value. Repetitive loading led to a falling IOP whether the foot was perfused or not.
CONCLUSION
Superimposed on a variable background IOP, increased perfusion and physiological loading caused a significant increase in subchondral IOP. Force was thereby transmitted through subchondral bone partly by hydraulic pressure. A falling IOP with repeat loading suggests that there is an intraosseous one-way valve. This offers a new understanding of subchondral perfusion physiology.
Topics: Animals; Ankle Joint; Biomechanical Phenomena; Cattle; Foot Joints; In Vitro Techniques; Male; Perfusion; Pressure; Serum; Transducers, Pressure; Weight-Bearing
PubMed: 32600340
DOI: 10.1186/s13018-020-01754-y -
BioMed Research International 2018Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear... (Review)
Review
Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal kidney preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ preservation paradigms: new concepts must emerge and the definition of a new range of adapted preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during preservation, and clear procedure for organ perfusion during machine preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.
Topics: Animals; Humans; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Practice Guidelines as Topic; Reperfusion Injury
PubMed: 30643824
DOI: 10.1155/2018/9206257 -
HPB : the Official Journal of the... Nov 2017This study aimed to identify the most effective solution for in situ perfusion/preservation of the pancreas in donation after brain death donors, in addition to optimal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This study aimed to identify the most effective solution for in situ perfusion/preservation of the pancreas in donation after brain death donors, in addition to optimal in situ flush volume(s) and route(s) during pancreas procurement.
METHODS
Embase, Medline and Cochrane databases were utilized (1980-2017). Articles comparing graft outcomes between two or more different perfusion/preservation fluids (University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK) and/or Celsior) were compared using random effects models where appropriate.
RESULTS
Thirteen articles were included (939 transplants). Confidence in available evidence was low. A higher serum peak lipase (standardized mean difference 0.47, 95% CI 0.23-0.71, I = 0) was observed in pancreatic grafts perfused/preserved with HTK compared to UW, but there were no differences in one-month pancreas allograft survivals or early thrombotic graft loss rates. Similarly, there were no significant differences in the rates of graft pancreatitis, thrombosis and graft survival between UW and Celsior solutions, and between aortic-only and dual aorto-portal perfusion.
CONCLUSION
UW cold perfusion may reduce peak serum lipase, but no quality evidence suggested UW cold perfusion improves graft survival and reduces thrombosis rates. Further research is needed to establish longer-term graft outcomes, the comparative efficacy of Celsior, and ideal perfusion volumes.
Topics: Adult; Cold Temperature; Female; Graft Survival; Humans; Male; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Pancreatectomy; Perfusion; Postoperative Complications; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Young Adult
PubMed: 28844527
DOI: 10.1016/j.hpb.2017.07.012 -
Transplantation Reviews (Orlando, Fla.) Apr 2023Evidence suggests that ventilation during ex vivo lung perfusion (EVLP) with a 'one-size-fits-all' strategy has the potential to cause lung injury which may only become... (Review)
Review
Evidence suggests that ventilation during ex vivo lung perfusion (EVLP) with a 'one-size-fits-all' strategy has the potential to cause lung injury which may only become clinically relevant in marginal lung allografts. EVLP induced- or accelerated lung injury is a dynamic and cumulative process reflecting the interplay of a number of factors. Stress and strain in lung tissue caused by positive pressure ventilation may be exacerbated by the altered properties of lung tissue in an EVLP setting. Any pre-existing injury may alter the ability of lung allografts to accommodate set ventilation and perfusion techniques on EVLP leading to further injury. This review will examine the effects of ventilation on donor lungs in the setting of EVLP. A framework for developing a protective ventilation technique will be proposed.
Topics: Humans; Lung Injury; Lung Transplantation; Lung; Perfusion; Tissue Donors
PubMed: 37099887
DOI: 10.1016/j.trre.2023.100762 -
Annals of Transplantation Aug 2021A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and... (Review)
Review
A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and improvement of marginal allografts. The most exciting development in the past decade has been continuous mechanical perfusion of livers with blood or preservation solution to mitigate ischemia-reperfusion injury in contrast to the current standard of static cold storage. Two variations of machine perfusion have emerged in clinical practice. During hypothermic oxygenated perfusion the liver is perfused using a red blood cell-free perfusate at 2-10°C. In contrast, normothermic machine perfusion mimics physiologic liver perfusion using a red blood cell-based solution at 35.5-037.5°C, offering a multitude of potential advantages. Putative effects of normothermic perfusion include abrogation of hyperfibrinolysis after reperfusion and inflammation, glycogen repletion, and regeneration of adenosine triphosphate. Research in normothermic machine perfusion focuses on development of biomarkers predicting allograft quality and susceptibility to ischemia-reperfusion injury. Moreover, normothermic perfusion of marginal allografts allows for application of a variety of therapeutic interventions potentially enhancing organ quality. Both methods need to be subjected to translational investigation and evaluation in clinical trials. A clear advantage is transformation of an emergency procedure at night into a planned daytime surgery. Current clinical trials suggest that normothermic perfusion not only increases the use of hepatic allografts but is also associated with milder ischemia-reperfusion injury, resulting in a reduced risk of early allograft dysfunction and less biliary complications, including ischemic cholangiopathy, compared to static cold storage. The aim of this review is to give a concise overview of normothermic machine perfusion and its current applications, benefits, and possible advances in the future.
Topics: Aged; Biomarkers; Humans; Liver; Liver Transplantation; Organ Preservation; Perfusion; Reperfusion Injury
PubMed: 34426566
DOI: 10.12659/AOT.931664 -
Perfuse and Reuse: A Low-Cost Three-Dimensional-Printed Perfusion Bioreactor for Tissue Engineering.Tissue Engineering. Part C, Methods Nov 2022This article describes fabrication of a customizable bioreactor, which comprises a perfusion system and coverslip-based tissue culture chamber that allow...
This article describes fabrication of a customizable bioreactor, which comprises a perfusion system and coverslip-based tissue culture chamber that allow centimeter-scale vascularized or otherwise canalized tissue constructs to be maintained in weeks long static and/or perfusion culture at an exceptionally low cost, with intermittent live imaging and media sampling capabilities. The perfusion system includes a reusable polydimethylsiloxane (PDMS) lid generated from a three-dimensional (3D)-printed poly-lactic acid (PLA) mold and several lengths of perfusion tubing. The coverslip tissue culture chamber includes PDMS components built with 3D-printed PLA molds, as well as 3D-printed PLA frames and glass coverslips that house perfusable hydrogel constructs. As proof of concept, we fabricated a vascularized hydrogel construct, which was subjected to static and perfusion tissue culture, as well as flow studies using fluorescent beads and widefield fluorescent microscopy. This system can be readily reproduced, promoting the advancement of tissue engineering and regenerative medicine research.
Topics: Tissue Engineering; Perfusion; Bioreactors; Hydrogels; Polyesters; Printing, Three-Dimensional; Tissue Scaffolds
PubMed: 36094108
DOI: 10.1089/ten.TEC.2022.0139 -
The Journal of Extra-corporeal... Jun 2017
Topics: Biomarkers; Cardiopulmonary Bypass; Fluid Therapy; Humans; Lactic Acid; Monitoring, Intraoperative; Oxygen; Patient Care Planning; Perfusion
PubMed: 28638165
DOI: No ID Found -
Veterinary Journal (London, England :... Jul 2022The endothelial glycocalyx (eGlx) lines the luminal surface of endothelial cells. It is critical in maintaining vascular health and when damaged contributes to many...
The endothelial glycocalyx (eGlx) lines the luminal surface of endothelial cells. It is critical in maintaining vascular health and when damaged contributes to many diseases. Its fragility makes studying the eGlx technically challenging. The current reference standard for eGlx visualisation, by electron microscopy using glutaraldehyde/Alcian blue perfusion fixation, has not been previously reported in dogs. Established techniques were applied to achieve visualisation of the eGlx in the microvasculature of reproductive tissue in five healthy dogs undergoing elective neutering. Uterine and testicular artery samples underwent perfusion fixation, in the presence of Alcian blue, prior to transmission electron microscopy imaging. Image processing software was used to determine eGlx depth. EGlx was visualised in the arteries of two dogs, one testicular and one uterine, with median (range) eGlx depths of 68.2 nm (32.1-122.9 nm) and 47.6 nm (26.1-129.4 nm) respectively. Study of the eGlx is technically challenging, particularly its direct visualisation in clinical samples. Further research is needed to develop more clinically applicable techniques to measure eGlx health.
Topics: Alcian Blue; Animals; Dogs; Endothelial Cells; Glycocalyx; Perfusion
PubMed: 35640795
DOI: 10.1016/j.tvjl.2022.105844 -
Experimental and Clinical... Dec 2015After the first clinical application of ex vivo lung perfusion in 2001, the technique has been used in many lung transplant centers worldwide. In addition, many... (Review)
Review
After the first clinical application of ex vivo lung perfusion in 2001, the technique has been used in many lung transplant centers worldwide. In addition, many modifications have been tested, leading to the development of various ex vivo lung perfusion systems and application protocols. Currently, the Lund protocol, the Toronto protocol, and Organ Care System Lung protocol are the clinically applied ex vivo lung perfusion protocols, based on the favorable results of the safety studies. Accordingly, the comparison among these EVLP systems and protocols should be an important research target, in order to provide the evidence based medical data that would recommend one protocol over the others. In this manuscript, the current experience with EVLP is reviewed and some molecular and clinical targets, that could be used to compare the various protocols of the technique, are introduced.
Topics: Biomarkers; Humans; Lung Transplantation; Organ Preservation; Perfusion
PubMed: 26643670
DOI: No ID Found