Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission

Liu, Wenyan; Yang, Fan; Ding, Hong-Fan; Han, Dan; Yan, Yang; Wu, Rongqian; Lv, Yi; Zheng, Xinglong

doi:10.1111/jcmm.17062

Cited by 26 publications

(21 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29,30 We showed that this customized setup can reduce IRI in the graft immediately after liver transplantation/reperfusion, measured by tissue injury evaluation and transaminase release. Other authors have shown similar results 31 of NMP on decreased oxidative stress, but this is the first time that IRI was scored in the graft after portal reperfusion, resembling the clinical scenario. Interestingly, this effect did not correlate with lower oxidation in liver tissue measured by MDA in our setup, perhaps due to hyper-oxygenation during NMP.…”

Section: F I G U R E 3 Nmp Summary Results Representation Of Arterial...supporting

confidence: 73%

Customized normothermic machine perfusion decreases ischemia–reperfusion injury compared with static cold storage in a porcine model of liver transplantation

et al. 2022

View full text Add to dashboard Cite

Background Liver transplantation has been demonstrated to be the best treatment for several liver diseases, while grafts are limited. This has caused an increase in waiting lists, making it necessary to find ways to expand the number of organs available for transplantation. Normothermic perfusion (NMP) of liver grafts has been established as an alternative to static cold storage (SCS), but only a small number of perfusion machines are commercially available. Methods Using a customized ex situ machine perfusion, we compared the results between ex situ NMP and SCS preservation in a porcine liver transplant model. Results During NMP, lactate concentrations were 80% lower after the 3‐h perfusion period, compared with SCS. Bile production had a 2.5‐fold increase during the NMP period. After transplantation, aspartate transaminase (AST) and alanine transaminase (ALT) levels were 35% less in the NMP group, compared to the SCS group. In pathologic analyses of grafts after transplant, tissue oxidation did not change between groups, but the ischemia–reperfusion injury score was lower in the NMP group. Conclusion NMP reduced hepatocellular damage and ischemia–reperfusion injury when compared to SCS using a customized perfusion machine. This could be an alternative for low‐income countries to include machine perfusion in their therapeutic options.

show abstract

Section: F I G U R E 3 Nmp Summary Results Representation Of Arterial...supporting

confidence: 73%

Customized normothermic machine perfusion decreases ischemia–reperfusion injury compared with static cold storage in a porcine model of liver transplantation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…A European single‐center study reported similar findings, with successful transplantation of up to 83% eNMP‐preserved livers that had initially been discarded 17,20 . However, these studies invariably suffered from selection bias, and the true contribution of eNMP to the increased organ utilization rate therefore remains obscure 30,31 . Although derived from non‐randomized trials, cumulative evidence for the value of NRP in DCD liver transplantation suggests that outcomes are improved with respect to IC (Table 3).…”

Section: What Do We Know About Dynamic Preservation?mentioning

confidence: 84%

“… 18 Surprisingly, to date, mechanistic studies dissecting the role of oxygen tension as a driver of mitochondrial injury at normothermic temperatures are unavailable. Nevertheless, metabolomics data from porcine and rat experiments of DCD liver transplantation suggest that NMP can reverse mitochondrial ischemic injury and restore mitochondrial function 30,31 …”

Section: How Does Dynamic Preservation Work?mentioning

confidence: 99%

“…In DCD donors, in situ dynamic preservation is initiated prior to the organ procurement, a method referred to as normothermic regional perfusion (NRP). 30,31 In this instance, after death has been confirmed, the donor vasculature is connected to an extracorporeal pump circuit that recirculates blood through the abdominal or thoracoabdominal compartment, while excluding the cerebral circulation.…”

Section: What Do We Know About Dynamic Preservation?mentioning

confidence: 99%

“…17,20 However, these studies invariably suffered from selection bias, and the true contribution of eNMP to the increased organ utilization rate therefore remains obscure. 30,31 Although derived from non-randomized trials, cumulative evidence for the value of NRP in DCD liver transplantation suggests that outcomes are improved with respect to IC (Table 3). A recent meta-analysis by De Beule et al showed that NRP reduced the IC frequency by 75%, although a reduction in post-transplant mortality was not seen.…”

Section: What Do We Know About Dynamic Preservation?mentioning

confidence: 99%

See 2 more Smart Citations

Dynamic liver preservation: Are we still missing pieces of the puzzle?

2022

View full text Add to dashboard Cite

To alleviate the persistent shortage of donor livers, high-risk liver grafts are increasingly being considered for liver transplantation. Conventional preservation with static cold storage falls short in protecting these high-risk livers from ischemia-reperfusion injury, as evident from higher rates of post-transplant complications such as early allograft dysfunction and ischemic cholangiopathy.Moreover, static cold storage does not allow for a functional assessment of the liver prior to transplantation. To overcome these limitations, dynamic strategies of liver preservation have been proposed, designed to provide a protective effect while allowing pre-transplant functional assessment. In this review, we discuss how different dynamic preservation strategies exert their effects, where we stand in assessing liver function and what challenges are lying ahead.

show abstract

A novel cytoprotective organ perfusion platform for reconstructing homeostasis of DCD liver while alleviating IRI injury

Lan,

Yu,

Ming

et al. 2024

Bioengineering & Transla Med

View full text Add to dashboard Cite

Pump is a vital component for expelling the perfusate in small animal isolated organ normothermic machine perfusion (NMP) systems whose flexible structure and rhythmic contraction play a crucial role in maintaining perfusion system homeostasis. However, the continuous extrusion forming with the rigid stationary shaft of the peristaltic pumps can damage cells, leading to metabolic disorders and eventual dysfunction of transplanted organs. Here, we developed a novel biomimetic blood‐gas system (BBGs) for preventing cell damage. This system mimics the cardiac cycle and features an adjustable inspiratory‐to‐expiratory (IE) ratio to mitigate acidosis caused by continuous oxygen inhalation. In our study, adipose stem cells (ADSCs) were cultured within the circulatory system for 10 min, 2, and 4 h. Compared to the peristaltic pump, the BBGs significantly reduced cell apoptosis and morphological injury while enhancing cell proliferation and adhesion. Additionally, when the supernatant from ADSCs was introduced to LPS‐induced macrophages for 24 h, the BBGs group demonstrated a more pronounced anti‐inflammatory effect, characterized by reduced M1 macrophage expression. Besides, with isolated rat livers from donation after circulatory death (DCD) perfusion with ADSCs for 6 h by the BBGs, we detected fewer apoptotic cells and a reduced inflammatory response, evidenced by down‐regulated TNF‐α expression. The development of BBGs demonstrates the feasibility of recreating physiological liquid–gas circulation in vitro, offering an alternative platform for isolated organ perfusion, especially for applications involving cell therapy.

show abstract

Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 26 publications

References 33 publications

Customized normothermic machine perfusion decreases ischemia–reperfusion injury compared with static cold storage in a porcine model of liver transplantation

Customized normothermic machine perfusion decreases ischemia–reperfusion injury compared with static cold storage in a porcine model of liver transplantation

Dynamic liver preservation: Are we still missing pieces of the puzzle?

A novel cytoprotective organ perfusion platform for reconstructing homeostasis of DCD liver while alleviating IRI injury

Contact Info

Product

Resources

About