Experimental Models in Liver Surgery

Jiménez‐Castro, Mónica B.; Elias-Miró, M.; Casillas-Ramírez, Araní; Peralta, Carmen A.

doi:10.5772/51829

Cited by 6 publications

(15 citation statements)

References 136 publications

(247 reference statements)

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“…However, it has been associated with delayed liver failure and poor prognosis in patients undergoing major hepatectomy in conditions of prolonged liver ischemia [1,13]. The global liver ischemia model with portal decompression provides an ideal simulation of the clinical condition of warm ischemia after the Pringle maneuver for liver resection and transplant [6,14]. The first successful shunt operation carried out in humans was by Vidal in 1903 [24].…”

Section: Global Hepatic Ischemia With Portocaval Decompressionmentioning

confidence: 99%

“…In most cases, in clinical practice, liver surgery involves both ischemia-reperfusion (I/R) injury and regeneration [1]. Liver I/R injury is a pathophysiological event that occurs during surgical interventions such as liver resection or liver transplantation (LT); it controls bleeding during parenchymal dissection and has a significant effect on liver function prognosis [2][3][4][5][6]. I/R injury is a twostage phenomenon in which cell damage due to hypoxia and the lack of biomechanical stimulus is exacerbated upon the restoration of oxygen delivery and shear stress [7].…”

Section: Introductionmentioning

confidence: 99%

“…Liver I/R injury involves great many factors and mediators. The associations between the signaling pathways are extremely complex, and at present, the events occurring between the start of reperfusion and the final outcome (either poor function or a nonfunctional liver graft) are not fully understood [6]. The extent and timing of ischemia, the type of liver undergoing I/R, and the existence of liver regeneration may alter the mechanisms of liver I/R injury and the effects of the treatment strategies assessed to date [12].…”

Section: Introductionmentioning

confidence: 99%

“…These models are valuable tools for elucidating the physiopathology of liver I/R injury and uncovering new therapeutic targets and drugs. A number of strategies for protecting the liver from I/R injury and for improving liver regeneration have been developed in animal models, some of which may find their way into clinical practice [6]. We stress that the type of ischemia (cold or warm) has an important influence in liver surgery, but most of the currently available reviews on the mechanisms of I/R do not distinguish between them [6].…”

Section: Introductionmentioning

confidence: 99%

“…A number of strategies for protecting the liver from I/R injury and for improving liver regeneration have been developed in animal models, some of which may find their way into clinical practice [6]. We stress that the type of ischemia (cold or warm) has an important influence in liver surgery, but most of the currently available reviews on the mechanisms of I/R do not distinguish between them [6]. In our view, this information may help to guide the design of future experimental models and treatment strategies in liver surgery for use in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Hepatic Regeneration Under Warm or Cold Ischemia Conditions: Controversies and New Approaches

Cornide‐Petronio¹,

Jiménez‐Castro²,

Bujaldon³

et al. 2019

Surgical Challenges in the Management of Liver Disease

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Ischemia-reperfusion (I/R) associated with hepatic resection and living related liver transplantation is an unsolved problem in clinical practice. Indeed, I/R induces damage and regenerative failure in clinical liver surgery. Signaling pathways regarding the pathophysiology of liver I/R and regeneration making clear distinction between situations of cold and warm ischemia, as well as liver regeneration with or without vascular occlusion, will be addressed. The different experimental models used to date to improve the postoperative outcomes in clinical liver surgery will be also described. Furthermore, the most updated therapeutic strategies, as well as the clinical and scientific controversies in the field, will be discussed. Such information may be useful to guide the design of better experimental models as well as the effective therapeutic strategies in liver surgery that can succeed in achieving its clinical application.

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Section: Global Hepatic Ischemia With Portocaval Decompressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hepatic Regeneration Under Warm or Cold Ischemia Conditions: Controversies and New Approaches

Cornide‐Petronio¹,

Jiménez‐Castro²,

Bujaldon³

et al. 2019

Surgical Challenges in the Management of Liver Disease

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Gastro-Enteropancreatic Neuroendocrine Tumor Cell Dynamics in Liver Microvasculature

et al. 2015

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For many cancers, liver metastasis is common and usually indicates poor prognosis. Gastro-enteropancreatic neuroendocrine tumors (GEPNETs) of the midgut are a heterogeneous group of cancers that typically remain asymptomatic until they metastasize to the liver. However, the mechanisms by which these usually indolent cancers establish distal metastasis remain unclear. To begin to elucidate this process, we performed standard in vitro assays to assess cell motility, transendothelial migration, and invasion using BON cells, a widely used model GEPNET cell line. In addition, transmission electron microscopy was used in combination with a novel ex vivo organ slice xenograft model to reveal ultrastructural details of the initial events of BON cell extravasation and re-distribution within the liver. The ultrastructural resolution of the extravasation process revealed the route, sequence, and time course by which tumor cells migrated from the sinusoidal lumen into the hepatic parenchyma in this organ slice model. Both standard in vitro assays and our organ slice model indicated that tumor cells migrated through the discontinuous sinusoidal endothelium to invade the liver parenchyma.

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Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage

et al. 2022

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Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)–dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21 KO model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation.

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Experimental Models in Liver Surgery

Cited by 6 publications

References 136 publications

Hepatic Regeneration Under Warm or Cold Ischemia Conditions: Controversies and New Approaches

Hepatic Regeneration Under Warm or Cold Ischemia Conditions: Controversies and New Approaches

Gastro-Enteropancreatic Neuroendocrine Tumor Cell Dynamics in Liver Microvasculature

Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage

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