			Home About us Contact

Hepatic Regeneration (hepatic + regeneration)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Surgery & Surgical Specialties	30%
Hepatology	23%

Selected Abstracts

Role of adult living donor liver transplantation in patients with hepatitis C

LIVER TRANSPLANTATION, Issue 10C 2003
Gregory T. Everson
Key points 1. Living donor liver transplantation (LDLT) is an option for patients with end-stage liver disease or hepatoma caused by chronic hepatitis C. 2. Reports from some, but not all, transplant centers indicate that hepatitis C may recur earlier, recurrence may be more severe, and graft loss caused by recurrent hepatitis C may be more frequent in LDLT compared with cadaveric transplantation. 3. Several unique characteristics of LDLT (versus cadaveric transplantation) may favor severe recurrence of hepatitis C. These include an increase in genetic similarity between donor and recipient, higher degree of HLA matching, greater systemic bioavailability of immunosuppressive agent, and hepatic regeneration. 4. Hepatic regeneration may promote the acceleration and severity of recurrent hepatitis C by enhancement of hepatitis C viral uptake by hepatocytes through stimulation of the low-density lipoprotein receptor and increase in activity of the internal ribosomal entry site. [source]

Tumor necrosis factor,like weak inducer of apoptosis is a mitogen for liver progenitor cells,,

HEPATOLOGY, Issue 1 2010
Janina E. E. Tirnitz-Parker
Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor,like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDE-treated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin,positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NF,B) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NF,B subunit by RNA interference. Conclusion: TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NF,B-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. (HEPATOLOGY 2010) [source]

Disruption of hepatic adipogenesis is associated with impaired liver regeneration in mice

HEPATOLOGY, Issue 6 2004
Eyal Shteyer
The liver responds to injury with regulated tissue regeneration. During early regeneration, the liver accumulates fat. Neither the mechanisms responsible for nor the functional significance of this transient steatosis have been determined. In this study, we examined patterns of gene expression associated with hepatic fat accumulation in regenerating liver and tested the hypothesis that disruption of hepatic fat accumulation would be associated with impaired hepatic regeneration. First, microarray-based gene expression analysis revealed that several genes typically induced during adipocyte differentiation were specifically upregulated in the regenerating liver prior to peak hepatocellular fat accumulation. These observations suggest that hepatic fat accumulation is specifically regulated during liver regeneration. Next, 2 methods were employed to disrupt hepatocellular fat accumulation in the regenerating liver. Because exogenous leptin supplementation reverses hepatic steatosis in leptin-deficient mice, the effects of leptin supplementation on liver regeneration in wild-type mice were examined. The data showed that leptin supplementation resulted in suppression of hepatocellular fat accumulation and impairment of hepatocellular proliferation during liver regeneration. Second, because glucocorticoids regulate cellular fat accumulation during adipocyte differentiation, the effects of hepatocyte-specific disruption of the glucocorticoid receptor were similarly evaluated. The results showed that hepatic fat accumulation and hepatocellular proliferation were also suppressed in mice with liver specific disruption of glucocorticoid receptor. In conclusion, suppression of hepatocellular fat accumulation is associated with impaired hepatocellular proliferation following partial hepatectomy, indicating that hepatocellular fat accumulation is specifically regulated during and may be essential for normal liver regeneration. (HEPATOLOGY 2004;40:1322,1332.) [source]

Effect of granulocyte-macrophage colony-stimulating factor on hepatic regeneration after 70% hepatectomy in normal and cirrhotic rats

HPB, Issue 2 2002
A Ero
Background Post-hepatectomy liver insufficiency is one of the most serious postoperative problems and its prevention is important after major hepatic resection, especially in the cirrhotic liver. Some growth factors and cytokines appear to play important roles in liver regeneration. In the present study we have investigated the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hepatic regeneration after 70% partial hepatectomy (PH) in cirrhotic and non-cirrhotic rats. Methods A rat model of liver cirrhosis was prepared using thioacetamide (TAA) (a dose of 20 mg/100 g body w, intraperitoneally) on three days a week for 12 weeks. Adult male rats were divided into four groups:Group 1 (n = 10) no cirrhosis and no GM-CSF; Group 2 (n = 10) no cirrhosis and GM-CSF; Group 3 (n = 10) cirrhosis and no GM-CSF; and Group 4 (n = 10) cirrhosis and GM-CSF. All the rats underwent a 70% hepatectomy, and GM-CSF was administrated immediately after operation in Groups 2 and 4. On postoperative days 2 and 7, fresh samples from the remnant liver were obtained to evaluate its regenerative capacity. The liver regenerative process was estimated by DNA synthesis, using flow cytometry. Results Proliferation index (PI) of hepatocytes at 48 h was higher in Group 4 rats than Group 3 rats (p < 0.05). On post-operative day 7, PI was elevated in Group 3 rats compared with Group 4 rats, but this difference was not statistically significant. In non-cirrhotic rats given GM-CSF, PI was increased compared with Group 1 rats at day 2 (p < 0.05), but not at day 7. Conclusions The findings suggest that the proliferative capacity of liver cells is impaired and delayed after 70% PH in cirrhotic rat liver. GM-CSF administration might enhance the liver PI in both normal and TAA-induced cirrhotic rats. [source]

Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010
M. B. Herrera
Abstract Several studies indicate that adult stem cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human liver stem cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an ,4 -integrin-dependent mechanism. However, MVs pre-treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA-dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre-treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets. [source]

The value of microsurgery in liver research

LIVER INTERNATIONAL, Issue 8 2009
Maria-Angeles Aller
Abstract The use of an operating microscope in rat liver surgery makes it possible to obtain new experimental models and improve the already existing macrosurgical models. Thus, microsurgery could be a very valuable technique to improve experimental models of hepatic insufficiency. In the current review, we present the microsurgical techniques most frequently used in the rat, such as the portacaval shunt, the extrahepatic biliary tract resection, partial and total hepatectomies and heterotopic and orthotopic liver transplantation. Hence, reducing surgical complications allows for perfecting the resulting experimental models. Thus, liver atrophy related to portacaval shunt, prehepatic portal hypertension secondary to partial portal vein ligation, cholestasis by resection of the extrahepatic biliary tract, hepatic regeneration after partial hepatectomies, acute liver failure associated with subtotal or total hepatectomy and finally complications derived from preservation or rejection in orthotopic and heterotopic liver transplantation can be studied in more standardized experimental models. The results obtained are therefore more reliable and facilitates the flow of knowledge from the bench to the bedside. Some of these microsurgical techniques, because of their simplicity, can be performed by researchers without any prior surgical training. Other more complex microsurgical techniques require in-depth surgical training. These techniques are ideal for achieving a complete surgical training and more select microsurgical models for hepatology research. [source]

Role of adult living donor liver transplantation in patients with hepatitis C

Regulatory effects of senescence marker protein 30 on the proliferation of hepatocytes

PATHOLOGY INTERNATIONAL, Issue 7 2001
Terunobu Ishigami
Senescence marker protein 30 (SMP 30) is preferentially expressed in the liver. One of its remarkable functions is the protection of cells against various injuries by enhancement of membrane calcium-pump activity. We analyzed the role of SMP 30 in hepatocyte proliferation. SMP 30 expression was decreased initially, then increased along with hepatic regeneration, after carbon tetrachloride (CCl4) administration. SMP 30 expression was decreased in the necrotic phase and then gradually increased. Its increase was slightly delayed just after the mitotic phase. These results lead us to speculate that mitoses of hepatic cells induce enhanced SMP 30 expression. In contrast, administration of lead nitrate (LN) as a hepatic mitogen induced a more stable increase of SMP 30 expression. To estimate the effect of SMP 30 on cell proliferation, we evaluated hepatic mitosis in wild-type and SMP 30-deficient knockout (KO) mice after CCl4 administration. We found an increase in mitotic numbers in hepatocytes of KO mice. This result suggests that SMP 30 has a suppressive effect on cell proliferation. Suppressive activity of SMP 30 cDNA was shown in cultured hepatoblastic cells. Our results suggest that SMP 30 performs a regulatory function in liver regeneration. [source]

Fulminant hepatic failure in the elderly: A clinicopathological study of autopsy cases aged over 65 years

PATHOLOGY INTERNATIONAL, Issue 2 2000
Motoji Sawabe
The pathology of fulminant hepatic failure (FHF) in the elderly is little known because of its very low frequency. Thirteen autopsy cases, all above 65 years of age (mean ± SD, 72 ± 6 years), and 10 younger control cases, all below 40 years of age (30 ± 7 years), were analyzed. The elderly group comprised 10 cases with subacute FHF and three cases with acute FHF, while the younger group comprised seven cases with subacute FHF and three cases with acute FHF. The most predominant pathological type in the elderly group was submassive hepatic necrosis (10 cases), followed by acute hepatitis with bridging hepatic necrosis (AH-BHN; two cases) and massive hepatic necrosis (one case). In two cases of submassive hepatic necrosis, hepatic regeneration seemed to be insufficient for the suggested history. The underlying diseases and terminal complications were significantly more frequent in the elderly group than in the younger group. In conclusion, the immune response in the elderly group is found to be strong enough to cause massive or submassive hepatic necrosis. However, impaired hepatic regeneration is occasionally observed in the elderly cases and AH-BHN is often lethal because of frequent underlying diseases and severe complications. [source]

Use of radiolabelled iododeoxyuridine as adjuvant treatment for experimental tumours of the liver

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2003
J. S. Zager
Background The aim of the study was to determine whether hepatic regeneration stimulates growth of tumour residing within the liver, and whether a difference in the rate of DNA synthesis in liver and tumour may be used to target cancer using the radiolabelled thymidine analogue 5-iodo-2,-deoxyuridine (IUdR). Methods Partial hepatectomy was performed on Buffalo rats bearing solitary nodules of syngeneic Morris hepatoma. Liver and tumour DNA synthesis was measured by incorporation of radioactive IUdR. [125I]IUdR was tested as an adjuvant therapy after hepatectomy in Buffalo rats bearing diffuse microscopic Morris hepatomas to simulate the clinical situation. Results Liver regeneration enhanced liver and tumour DNA synthesis as measured by incorporation of radioactive IUdR. Liver DNA synthesis returned to baseline by 7 days, whereas tumour DNA synthesis remained above baseline level. Hepatectomy enhanced the growth of microscopic liver tumours. [125I]IUdR (250 µCi or 1 mCi/kg) administered 4 days after hepatectomy significantly reduced tumour growth without signs of systemic toxicity or liver dysfunction. Conclusion The local environment of the regenerating liver stimulates tumour growth. The thymidine analogue [125I]IUdR may be used preferentially to target tumour DNA synthesis in the regenerating liver, and may prove useful as an adjuvant therapy for hepatic tumours after surgical resection. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Segmental nature of the porcine liver and its potential as a model for experimental partial hepatectomy,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2003
F. G. Court
Background: In-depth knowledge of pig liver anatomy allows potential research into segmental liver resections and hepatic regeneration, as well as liver transplantation techniques. The segmental anatomy, however, remains largely unknown. This study aimed to delineate the segmental anatomy of the porcine liver in comparison with that of the human. Methods: The segmental anatomy of the porcine liver was determined using acrylic injection casting of ex vivo pig livers, allowing the arterial, venous and biliary supply to be visualized directly. This was correlated using multi-slice computed tomography (CT) and three-dimensional reconstructions. Results: Although the external morphology of the porcine liver differs from that of the human, the segmental anatomy is remarkably similar in term of its vascularity and biliary tree. Conclusion: Acrylic casting of the porcine liver accurately delineates the vascular and biliary anatomy, and is a useful tool for performing experimental liver surgery. The similarities between porcine and human segmental anatomy allow domestic swine to be used as a comparable model. Three-dimensional CT reconstructions can also accurately visualize the anatomy and may be used to perform virtual surgery, or to assess segmental volumes. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]