Clinical Outcomes and Genetic Expression Profile in Human Liver Graft Dysfunction During Ischemia/Reperfusion Injury

Paulino, Jorge; Vigia, Emanuel; Marcelino, Paulo; Abade, O.; Sobral, João; Ligeiro, Dário; Carvalho, A.; Alves, Marta; Papoila, Ana Luísa; Trindade, Hélder; Barroso, Eduardo

doi:10.1016/j.transproceed.2015.03.025

Cited by 3 publications

(2 citation statements)

References 34 publications

(26 reference statements)

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“…Liver transplantation is the standard therapy for end-stage liver disease 1 . At present, almost all transplanted livers suffer ischemia during cold preservation and subsequent reperfusion injury 2 , posing a huge challenge to the functional recovery of donor livers and the prognosis of recipients. The mechanism involved in ischemia–reperfusion injury (IRI) is complex, including changes in a variety of cellular components, inflammatory factors, and mediators 3 – 5 .…”

Section: Introductionmentioning

confidence: 99%

Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

Wang

et al. 2021

Cell Death Dis

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Ischemia–reperfusion injury (IRI) remains the major reason for impaired donor graft function and increased mortality post-liver transplantation. The mechanism of IRI involves multiple pathophysiological processes and numerous types of cells. However, a systematic and comprehensive single-cell transcriptional profile of intrahepatic cells during liver transplantation is still unclear. We performed a single-cell transcriptome analysis of 14,313 cells from liver tissues collected from pre-procurement, at the end of preservation and 2 h post-reperfusion. We made detailed annotations of mononuclear phagocyte, endothelial cell, NK/T, B and plasma cell clusters, and we described the dynamic changes of the transcriptome of these clusters during IRI and the interaction between mononuclear phagocyte clusters and other cell clusters. In addition, we found that TNFAIP3 interacting protein 3 (TNIP3), specifically and highly expressed in Kupffer cell clusters post-reperfusion, may have a protective effect on IRI. In summary, our study provides the first dynamic transcriptome map of intrahepatic cell clusters during liver transplantation at single-cell resolution.

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Section: Introductionmentioning

confidence: 99%

Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

Wang

et al. 2021

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Liver transplantation is the standard therapy for end-stage liver disease 1 . At present, almost all transplanted livers suffer ischemia during cold preservation and subsequent reperfusion injury 2 , posing a huge challenge to the functional recovery of donor livers and the prognosis of recipients. The mechanism involved in ischemia-reperfusion injury (IRI) is complex, including changes in a variety of cellular components, inflammatory factors and mediators [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

Wang

et al. 2021

Preprint

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Ischemia-reperfusion injury (IRI) remains the major reason for impaired donor graft function and increased mortality post-liver transplantation. The mechanism of IRI involves multiple pathophysiological processes and numerous types of cells. However, a systematic and comprehensive single-cell transcriptional profile of intrahepatic cells during liver transplantation is still unclear. We performed a single-cell transcriptome analysis of 14,313 cells from liver tissues collected from pre-procurement, at the end of preservation and 2 h post-reperfusion. We made detailed annotations of mononuclear phagocyte, endothelial cell, NK/T, B and plasma cell clusters, and we described the dynamic changes of the transcriptome of these clusters during IRI and the interaction between mononuclear phagocyte clusters and other cell clusters. In addition, we found that TNFAIP3 interacting protein 3 (TNIP3), specifically and highly expressed in Kupffer cell clusters post-reperfusion, may have a protective effect on IRI. In summary, our study provides the first dynamic transcriptome map of intrahepatic cell clusters during liver transplantation at single-cell resolution.

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The Role of Ischemia/Reperfusion Injury in Early Hepatic Allograft Dysfunction

et al. 2020

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Liver transplantation (LT) is the only available curative treatment for patients with end‐stage liver disease. Early allograft dysfunction (EAD) is a life‐threatening complication of LT and is thought to be mediated in large part through ischemia/reperfusion injury (IRI). However, the underlying mechanisms linking IRI and EAD after LT are poorly understood. Most previous studies focused on the clinical features of EAD, but basic research on the underlying mechanisms is insufficient, due, in part, to a lack of suitable animal models of EAD. There is still no consensus on definition of EAD, which hampers comparative analysis of data from different LT centers. IRI is considered as an important risk factor of EAD, which can induce both damage and adaptive responses in liver grafts. IRI and EAD are closely linked and share several common pathways. However, the underlying mechanisms remain largely unclear. Therapeutic interventions against EAD through the amelioration of IRI is a promising strategy, but most approaches are still in preclinical stages. To further study the mechanisms of EAD and promote collaborations between LT centers, optimized animal models and unified definitions of EAD are urgently needed. Because IRI and EAD are closely linked, more attention should be paid to the underlying mechanisms and the fundamental relationship between them. Ischemia/reperfusion–induced adaptive responses may play a crucial role in the prevention of EAD, and more preclinical studies and clinical trials are urgently needed to address the current limitation of available therapeutic interventions.

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Clinical Outcomes and Genetic Expression Profile in Human Liver Graft Dysfunction During Ischemia/Reperfusion Injury

Cited by 3 publications

References 34 publications

Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution

The Role of Ischemia/Reperfusion Injury in Early Hepatic Allograft Dysfunction

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