Ex vivo liver perfusion

There is a growing body of evidence that ER stress and the unfolded protein response (UPR) play a key role in numerous diseases. Impaired liver perfusion and ER stress often accompany each other in liver diseases. However, the exact impact of ER stress and UPR on the hepatic perfusion is not fully understood. The aim of this study was to disclose the effect of ER stress and UPR on the size of liver vessels and on the levels of Ca2+ and nitric oxide (NO), critical regulators of vascular tonus. This study was carried out in precisely cut liver tissue slices...

Acute lung injury is a common respiratory disease characterized by diffuse alveolar injury and interstitial edema, as well as a hyperinflammatory response, lung cell damage and oxidative stress. Foxq1, a member of the FOX family of transcription factors, is expressed in various tissues, such as the lungs, liver, and kidneys, and contributes to various biological processes, such as stress, metabolism, cell cycle arrest, and aging-related apoptosis. However, the role of Foxq1 in acute lung injury is unknown. We constructed ex vivo and in vivo acute lung injury models by lipopolysaccharide tracheal perfusion of ICR mice and conditioned medium stimulation of injured MLE-12 cells...

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon...

BACKGROUND: Microvascular visualization is crucial in understanding the mechanisms of several pathologies. For instance, visualization of the tumor microenvironment is important in understanding angiogenesis and role in cancer progression. Visualization would provide insights to cancer diagnosis, predicting metastatic growth, and evaluating therapeutic protocols. Similarly, understanding the microvascular network could be beneficial for study of degenerative diseases and tissue repair...

BACKGROUND: Normothermic machine perfusion (NMP) allows for the assessment and resuscitation of ex-vivo human livers prior to transplantation. Commercially available NMP systems are closed circuits that accumulate metabolic waste and cytokines over time, potentially limiting organ preservation times. Dialysis has been proposed as a method to remove waste and excess fluid from such systems. This study aimed to demonstrate the utility of integrating dialysis into a commercially available system by quantifying solute removal...

PURPOSE OF REVIEW: The number of patients on the liver transplant waitlist continues to grow and far exceeds the number of livers available for transplantation. Normothermic machine perfusion (NMP) allows for ex-vivo perfusion under physiologic conditions with the potential to significantly increase organ yield and expand the donor pool. RECENT FINDINGS: Several studies have found increased utilization of donation after cardiac death and extended criteria brain-dead donor livers with implementation of NMP, largely due to the ability to perform viability testing during machine perfusion...

Ex vivo normothermic machine perfusion (NMP) preserves donor organs and permits real-time assessment of allograft health, but the most effective indicators of graft viability are uncertain. Mitochondrial DNA (mtDNA), released consequent to traumatic cell injury and death, including the ischemia-reperfusion injury inherent in transplantation, may meet the need for a biomarker in this context. We describe a real time PCR-based approach to assess cell-free mtDNA during NMP as a universal biomarker of allograft quality...

In the early stages of liver carcinogenesis, rare hepatocytes and cholangiocytes are transformed into preneoplastic cells, which can progressively acquire a neoplastic phenotype, favored by the failure of natural antitumor immunosurveillance. The detailed study of both hepatic parenchymal (e.g., hepatocytes) and non-parenchymal cells (NPCs), such as immune cells, could help understand the cellular microenvironment surrounding these pre-cancerous and neoplastic lesions.Cultures of primary hepatocytes are of interest in various biomedical research disciplines, serving as an ex vivo model for liver physiology...

BACKGROUND Ischemia/reperfusion injury (IRI) is an inherent problem in organ transplantation, owing to the obligate period of ischemia that organs must endure. Cyclosporine A (CsA), though better know as an immunosuppressant, has been shown to mitigate warm IRI in a variety of organ types, including the liver. However, there is little evidence for CsA in preventing hepatic IRI in the transplant setting. MATERIAL AND METHODS In the present study, we tested the effect of CsA on hepatic IRI in a large-animal ex vivo model of donation after circulatory death (DCD)...

Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion...

Ischemia is a major limiting factor in Vascularized Composite Allotransplantation (VCA) as irreversible muscular injury can occur after as early as 4-6 hours of static cold storage (SCS). Organ preservation technologies have led to the development of storage protocols extending rat liver ex vivo preservation up to 4 days. Development of such a protocol for VCAs has the added challenge of inherent ice nucleating factors of the graft, therefore this study focused on developing a robust protocol for VCA supercooling...

BACKGROUND: Hepatic steatosis is the leading cause of discarded liver grafts. Defatting steatotic liver grafts using drug combinations during ex vivo normothermic machine perfusion (NMP) has been reported. However, the effectiveness of NMP in reducing fat content using epigallocatechin gallate (EGCG) as a single defatting agent and its effect on lipid metabolism are poorly investigated. METHODS: In this study, an NMP system was set up to perfuse a steatotic liver from a rat model with 10 mM EGCG...

BACKGROUND: Ex situ machine perfusion facilitates the assessment of livers prior to transplantation. However, currently available markers of liver function poorly predict long-term graft function. Indocyanine green (ICG) is a liver-specific dye which, although common in vivo, has never been comprehensively evaluated for the assessment of graft quality during ex situ machine perfusion. This study aimed to assess the utility of ICG in the ex situ setting. METHODS: Using a customized long-term perfusion system, human livers that were not suitable for transplantation were perfused using a red cell-based perfusate...

Ex vivo machine perfusion is rapidly growing in utility during solid organ transplantation. This form of organ preservation is transforming how organs are allocated and expanding the definition of what is considered a suitable organ for transplantation in comparison to traditional static cold storage. All major organs (heart, lung, liver, kidney) have been influenced by this advanced method of organ preservation. This technology also serves as an unprecedented platform for effective administration of advanced therapeutics, including gene therapies, during organ transplantation to optimize and recondition organs ex vivo in an isolated fashion...

Optical imaging techniques such as spectral imaging show promise for the assessment of tissue health during surgery; however, the validation and translation of such techniques into clinical practise is limited by the lack of representative tissue models. In this paper, we demonstrate the application of an organ perfusion machine as an ex vivo tissue model for optical imaging. Three porcine livers are perfused at stepped blood oxygen saturations. Over the duration of each perfusion, spectral data of the tissue are captured via diffuse optical spectroscopy and multispectral imaging...

Liver transplantation indications continue to evolve in North America. Several recent changes have occurred in the field with changes in the allocation system, new performance metrics, expansion of transplant oncology, and utilization of ex vivo perfusion devices and techniques. Deceased donor liver transplantation continues to be the primary modality of liver transplantation in North America, with an ongoing focus on advancing the use of living donor liver transplantation, especially in those patients who may not have favorable access to deceased donor allografts...

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BACKGROUND & AIMS: Liver paracrine signaling from liver sinusoid endothelial cells to hepatocytes in response to mechanical stimuli is crucial in highly coordinated liver regeneration. Interstitial flow through the fenestrated endothelium inside the space of Disse potentiates the role of direct exposure of hepatocytes to fluid flow in the immediate regenerative responses after partial hepatectomy, but the underlying mechanisms remain unclear. METHODS: Mouse liver perfusion was used to identify the effects of interstitial flow on hepatocyte proliferation ex vivo ...

No abstract text is available yet for this article.

BACKGROUND: Ex vivo normothermic machine perfusion (NMP) is an organ preservation technique that enables an extended assessment of graft suitability before liver transplantation (LT). Established monitoring protocols used during NMP vary significantly in their assessment of transplant suitability when applied to the same grafts. Graft-derived cell-free DNA (gdcfDNA) analysis is an emerging tool for monitoring graft health post-transplantation. We investigated the feasibility of monitoring gdcfDNA during NMP for LT in a proof-of-concept, observational study...