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A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration.

Dhar DK, Mohammad GH, Vyas S, Broering DC, Malago M - Ann Surg Innov Res (2015)

Bottom Line: To have an insight into the mechanism of ALPPS associated liver regeneration, we reproduced a rat model of ALPPS and compared the results with the PVL group.An early regeneration in the ALPPS group coincided with an early entry of hepatocytes into the cell proliferation phase, a significant increase in portal pressure and increase in hepatic enzymes in the ALPPS group compared with the PVL group.This unique rat model of ALPPS would help to improve our understanding about the liver generation process and also will help in further refinement of the ALPPS procedure for the clinical benefit.

View Article: PubMed Central - PubMed

Affiliation: Institute for Liver and Digestive Health, Royal Free Hospital, University College London, Pond Street, London, NW3 2PF UK ; Department of Organ Transplantation Centre and Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03 P.O. Box 3354, Riyadh, 11211 Saudi Arabia.

ABSTRACT

Background: Liver resection is the mainstay of treatment for most of the liver tumors. Liver has a unique capability to restore the lost volume following resection, however, most of the primary tumors grow in a liver with preexisting parenchymal diseases and secondary tumors often present in multiple liver lobes precluding a safe curative resection. Two-stage hepatectomy and portal vein ligation (PVL) are used to achieve a safer future remnant liver volume (FRLV), however, these procedures take several weeks to achieve adequate FRLV. A recently introduced faster alternative two-stage hepatectomy, also know as associated liver partitioning and portal vein ligation for staged hepatectomy (ALPPS), produces a desirable FRLV in days.

Methods: To have an insight into the mechanism of ALPPS associated liver regeneration, we reproduced a rat model of ALPPS and compared the results with the PVL group.

Results: Our results convincingly showed an advantage of the ALPPS procedure over PVL group in terms of early regeneration, however, in 1-week time the amount of regeneration was comparable. An early regeneration in the ALPPS group coincided with an early entry of hepatocytes into the cell proliferation phase, a significant increase in portal pressure and increase in hepatic enzymes in the ALPPS group compared with the PVL group. According to the protein array evaluation of 29 cytokines/chemokines, cytokine induced neutrophil chemoattractant-1 had the highest expression whereas IL-6 had the highest fold (>6 vs PVL group) expression at the early phase of regeneration in the ALPPS group.

Conclusions: This unique rat model of ALPPS would help to improve our understanding about the liver generation process and also will help in further refinement of the ALPPS procedure for the clinical benefit.

No MeSH data available.


Related in: MedlinePlus

The top 5 (a) panels show the relative expression of cytokines/chemokines in the liver tissue whose expression were more than twice in the ALPPS group than in the PVL group at early hours of liver regeneration (24 h). Whereas bottom three panels (b) show the expression of proteins whose expression was more than twice at 48 h time pint in the ALPPS group than in the PVL group
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Fig6: The top 5 (a) panels show the relative expression of cytokines/chemokines in the liver tissue whose expression were more than twice in the ALPPS group than in the PVL group at early hours of liver regeneration (24 h). Whereas bottom three panels (b) show the expression of proteins whose expression was more than twice at 48 h time pint in the ALPPS group than in the PVL group

Mentions: To evaluate the possible mechanism of early regenerative response in the ALPPS group, next we looked at the expression of a battery of cytokines/chemokines and growth factors at the tissue level. We used a proteome array kit to examine the expression profile of 29 cytokines/cytokines in liver tissue samples. The list of the proteins with their mean OD values is shown in Additional file 3: Table S1. We have divided them into early responsive or late responsive proteins depending on whether the expression of the proteins in the ALPPS group was higher at 24 or 48 h time points. Figure 6 shows the mean optical density (OD) values of the proteins whose expressions in the ALPPS group were more than twice than the expression in the PVL group. Among all of the cytokines, the cytokine-induced neutrophil chemoattractant -1 (CINC-1) had the strongest expression whereas the largest difference in expression between the ALPPS and PVL group was in interleukin-6 (IL-6) expression with more than 6-fold higher expression in the ALPPS group than in the PVL group at 24 h. Besides IL-6 and CINC-1, (interleukin-2)IL-2, (interleukin-13) IL-13 and macrophage inflammatory protein 1alpha (MIP-1a) expressions were higher(>2 fold) in the ALPPS group at 24 h time point than in the PVL group (Fig. 6a). In contrast, only granulocyte macrophage colony stimulating factor (GM-CSF) had more than 2-fold expression in the PVL group than in ALPPS group at 24 h. Also we noticed expression of granulocyte macrophage colony stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and interferon gamma (IFN-g) with late peaks at 48 h in the ALPPS group when compared with the PVL group (Fig. 6b).Fig. 6


A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration.

Dhar DK, Mohammad GH, Vyas S, Broering DC, Malago M - Ann Surg Innov Res (2015)

The top 5 (a) panels show the relative expression of cytokines/chemokines in the liver tissue whose expression were more than twice in the ALPPS group than in the PVL group at early hours of liver regeneration (24 h). Whereas bottom three panels (b) show the expression of proteins whose expression was more than twice at 48 h time pint in the ALPPS group than in the PVL group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4631081&req=5

Fig6: The top 5 (a) panels show the relative expression of cytokines/chemokines in the liver tissue whose expression were more than twice in the ALPPS group than in the PVL group at early hours of liver regeneration (24 h). Whereas bottom three panels (b) show the expression of proteins whose expression was more than twice at 48 h time pint in the ALPPS group than in the PVL group
Mentions: To evaluate the possible mechanism of early regenerative response in the ALPPS group, next we looked at the expression of a battery of cytokines/chemokines and growth factors at the tissue level. We used a proteome array kit to examine the expression profile of 29 cytokines/cytokines in liver tissue samples. The list of the proteins with their mean OD values is shown in Additional file 3: Table S1. We have divided them into early responsive or late responsive proteins depending on whether the expression of the proteins in the ALPPS group was higher at 24 or 48 h time points. Figure 6 shows the mean optical density (OD) values of the proteins whose expressions in the ALPPS group were more than twice than the expression in the PVL group. Among all of the cytokines, the cytokine-induced neutrophil chemoattractant -1 (CINC-1) had the strongest expression whereas the largest difference in expression between the ALPPS and PVL group was in interleukin-6 (IL-6) expression with more than 6-fold higher expression in the ALPPS group than in the PVL group at 24 h. Besides IL-6 and CINC-1, (interleukin-2)IL-2, (interleukin-13) IL-13 and macrophage inflammatory protein 1alpha (MIP-1a) expressions were higher(>2 fold) in the ALPPS group at 24 h time point than in the PVL group (Fig. 6a). In contrast, only granulocyte macrophage colony stimulating factor (GM-CSF) had more than 2-fold expression in the PVL group than in ALPPS group at 24 h. Also we noticed expression of granulocyte macrophage colony stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and interferon gamma (IFN-g) with late peaks at 48 h in the ALPPS group when compared with the PVL group (Fig. 6b).Fig. 6

Bottom Line: To have an insight into the mechanism of ALPPS associated liver regeneration, we reproduced a rat model of ALPPS and compared the results with the PVL group.An early regeneration in the ALPPS group coincided with an early entry of hepatocytes into the cell proliferation phase, a significant increase in portal pressure and increase in hepatic enzymes in the ALPPS group compared with the PVL group.This unique rat model of ALPPS would help to improve our understanding about the liver generation process and also will help in further refinement of the ALPPS procedure for the clinical benefit.

View Article: PubMed Central - PubMed

Affiliation: Institute for Liver and Digestive Health, Royal Free Hospital, University College London, Pond Street, London, NW3 2PF UK ; Department of Organ Transplantation Centre and Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03 P.O. Box 3354, Riyadh, 11211 Saudi Arabia.

ABSTRACT

Background: Liver resection is the mainstay of treatment for most of the liver tumors. Liver has a unique capability to restore the lost volume following resection, however, most of the primary tumors grow in a liver with preexisting parenchymal diseases and secondary tumors often present in multiple liver lobes precluding a safe curative resection. Two-stage hepatectomy and portal vein ligation (PVL) are used to achieve a safer future remnant liver volume (FRLV), however, these procedures take several weeks to achieve adequate FRLV. A recently introduced faster alternative two-stage hepatectomy, also know as associated liver partitioning and portal vein ligation for staged hepatectomy (ALPPS), produces a desirable FRLV in days.

Methods: To have an insight into the mechanism of ALPPS associated liver regeneration, we reproduced a rat model of ALPPS and compared the results with the PVL group.

Results: Our results convincingly showed an advantage of the ALPPS procedure over PVL group in terms of early regeneration, however, in 1-week time the amount of regeneration was comparable. An early regeneration in the ALPPS group coincided with an early entry of hepatocytes into the cell proliferation phase, a significant increase in portal pressure and increase in hepatic enzymes in the ALPPS group compared with the PVL group. According to the protein array evaluation of 29 cytokines/chemokines, cytokine induced neutrophil chemoattractant-1 had the highest expression whereas IL-6 had the highest fold (>6 vs PVL group) expression at the early phase of regeneration in the ALPPS group.

Conclusions: This unique rat model of ALPPS would help to improve our understanding about the liver generation process and also will help in further refinement of the ALPPS procedure for the clinical benefit.

No MeSH data available.


Related in: MedlinePlus