Rodent models of hepatic ischemia–reperfusion injury: time and percentage-related pathophysiological mechanisms

Karatzas, Theodore; Neri, Anna-Aikaterini; Baibaki, Maria-Eleni; Dontas, Ismene

doi:10.1016/j.jss.2014.06.024

Cited by 49 publications

(37 citation statements)

References 90 publications

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“…Besides transplantation models, numerous experimental approaches are known and used to investigate the phenomenon and mechanisms of transplantation injury [110], small-for-size syndrome [49,60], immunology/rejection [111], cold/warm ischemia-reperfusion [110,112,113], and regeneration of the liver [60,114]. …”

Section: Place Of Rat Olt and P-olt Models In Transplantation Researchmentioning

confidence: 99%

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

Czigány

Iwasaki²,

Yagi³

et al. 2015

Eur Surg Res

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Background: Due to a worldwide shortage of donor organs for liver transplantation, alternative approaches, such as split and living donor liver transplantations, were introduced to increase the donor pool and reduce mortality on liver transplant waiting lists. Numerous details concerning the mechanisms and pathophysiology of liver regeneration, small-for-size syndrome, rejection, and tolerance in partial liver transplantation facilitated the development of various animal models. The high number of preclinical animal studies contributed enormously to our understanding of many clinical aspects of living donor and partial liver transplantations. Summary: Microsurgical rat models of partial orthotopic liver transplantation are well established and widely used. Nevertheless, several issues regarding this procedure are controversial, not clarified, or not yet properly standardized (graft rearterialization, size reduction techniques, etc.). The major aim of this literature review is to give the reader a current overview of rat orthotopic liver transplantation models with a special focus on partial liver transplantation. The aspects of model evolution, microsurgical training, and different technical problems are analyzed and discussed in detail. Our further aim in this paper is to elaborate a detailed publication guide in order to improve the quality of reporting in the field of rat liver transplantation according to the ARRIVE guidelines and the 3R principle. Key Messages: Partial orthotopic liver transplantation in rats is an indispensable, reliable, and cost-efficient model for transplantation research. A certain consensus on different technical issues and a significant improvement in scientific reporting are essential to improve transparency and comparability in this field as well as to foster refinement.

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Section: Place Of Rat Olt and P-olt Models In Transplantation Researchmentioning

confidence: 99%

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

Czigány

Iwasaki²,

Yagi³

et al. 2015

Eur Surg Res

View full text Add to dashboard Cite

show abstract

“…It contributes to severe liver injury and dysfunction of the liver3 Hepatic I/R injury leads to the upregulation of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6456. Hepatic I/R injury is a common clinical occurrence that threatens the health of patients, underscoring the need to identify effective measures to protect against I/R injury.…”

mentioning

confidence: 99%

The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway

Liu

Zhang

et al. 2017

Sci Rep

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Hepatic ischemia/reperfusion (I/R) injury, which can result in severe liver injury and dysfunction, occurs in a variety of conditions such as liver transplantation, shock, and trauma. Cell death in hepatic I/R injury has been linked to apoptosis and autophagy. Shikonin plays a significant protective role in ischemia/reperfusion injury. The purpose of the present study was to investigate the protective effect of shikonin on hepatic I/R injury and explore the underlying mechanism. Mice were subjected to segmental (70%) hepatic warm ischemia to induce hepatic I/R injury. Two doses of shikonin (7.5 and 12.5 mg/kg) were administered 2 h before surgery. Balb/c mice were randomly divided into four groups: normal control, I/R, and shikonin preconditioning at two doses (7.5 and 12.5 mg/kg). The serum and liver tissues were collected at three time points (3, 6, and 24 h). Shikonin significantly reduced serum AST and ALT levels and improved pathological features. Shikonin affected the expression of Bcl-2, Bax, caspase 3, caspase 9, Beclin-1, and LC3, and upregulated PI3K and p-Akt compared with the levels in the I/R group. Shikonin attenuated hepatic I/R injury by inhibiting apoptosis and autophagy through a mechanism involving the activation of PI3K/Akt signaling.

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“…Ischemia-reperfusion injury is characterized by induction of oxidative stress, parenchymal cell apoptosis, and immune activation. 26 Our findings suggest that for orthotopic liver organoid implantation to succeed clinically, the acute inflammatory response induced by tissue injury from the implantation procedure, and potentially from ischemia-reperfusion, must be minimized. Various approaches aimed at reducing the inflammatory consequences of tissue injury are currently under investigation, including pre-operative conditioning, administration of anti-oxidants, nitric oxide agonists, anti-apoptotic and anti-inflammatory agents.…”

Section: Discussionmentioning

confidence: 82%

“…Ischemia-reperfusion injury is an important cause of organ dysfunction after major liver resections and liver transplantation. 26 Liver organoids may have experienced ischemia-reperfusion as a consequence of transfer from the bioreactor followed by subsequent reperfusion by blood released from disrupted sinusoids at the implantation site. Our data showed that viability of single-cells was better than organoids at 1 hour after implantation, suggesting that organoids may be more vulnerable to ischemia.…”

Section: Discussionmentioning

confidence: 99%

Direct orthotopic implantation of hepatic organoids

Zhou

Lolas

Chang

2017

Journal of Surgical Research

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Background Liver organoids show promise for development as a tissue replacement therapy for patients with end-stage liver disease, but efficient methods for introducing organoids into host livers have not been established. In this study, we aimed to develop a surgical technique to implant hepatic organoids into the liver and assess their engraftment. Methods Donor hepatocytes were isolated from ROSA26 C57BL/6 mice so that engrafted cells, when implanted into wild-type mice, could be easily identified by Xgal staining. Hepatic organoids were generated by three-dimensional culture in rotating wall vessel bioreactors. We qualitatively and quantitatively compared organoid engraftment to that of single-cell hepatocyte transplants. In addition, we determined the effect of adding stellate cells to hepatocytes to form co-aggregated organoids and the effect of partial hepatectomy of the host liver on organoid engraftment. Results Direct orthotopic implantation of hepatic organoids within a hepatotomy site resulted in local engraftment of exogenous hepatocytes with limited durability. Hepatocyte-stellate cell organoids produced more extracellular matrix but did not significantly improve engraftment compared to hepatocyte-alone organoids. Partial hepatectomy of the host liver led to significantly decreased engraftment of organoids. Survival of organoids was limited by the presence of apoptotic hepatocytes within organoids as early as 1 hour after implantation. Organoids eventually became necrotic and elicited a chronic inflammatory giant cell reaction similar to a foreign body response. Conclusion With additional organoid and host factor optimization, direct orthotopic implantation of hepatic organoids may be an approach to introduce large numbers of exogenous hepatocytes into recipient livers.

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Rodent models of hepatic ischemia–reperfusion injury: time and percentage-related pathophysiological mechanisms

Cited by 49 publications

References 90 publications

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway

Direct orthotopic implantation of hepatic organoids

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