The portal lobule in rat liver fibrosis: A re-evaluation of the liver unit

Bhunchet, Ekapot; Wake, Kanako

doi:10.1002/hep.510270223

Cited by 33 publications

(21 citation statements)

References 21 publications

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“…The terminal branch(es) of portal veins can be demonstrated inside larger foci, and the central veins are pushed aside. This is not surprising, considering that others 22,23 and we demonstrated that the foci are the descendant of canals of Hering-derived oval cells, which are always arranged in a radial fashion around the portal tracts. It seems that oval cells preserving their original periportal position and connections transform into small hepatocytes and constitute the foci.…”

Section: Discussionsupporting

confidence: 75%

“…Though the classical lobule is organized around a central vein and the portal branches are at the periphery, a fully developed focus is more similar to the so-called portal lobule. 22 It should be kept in mind that the healthy liver lobule is demarcated by approximately six portal tracts. Thereby, an individual focus does not turn into a hepatic lobule, but more foci can contribute to the build-up of a regenerated liver lobule.…”

Section: Discussionmentioning

confidence: 99%

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Structural analysis of oval-cell–mediated liver regeneration in rats

et al. 2012

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We have analyzed the architectural aspects of progenitor-cell-driven regenerative growth in rat liver by applying the 2-acetaminofluorene/partial hepatectomy experimental model. The regeneration is initiated by the proliferation of so-called oval cells. The oval cells at the proximal tips of the ductules have a more differentiated phenotype and higher proliferative rate. This preferential growth results in the formation of a seemingly random collection of small hepatocytes, called foci. These foci have no clonal origin, but possess a highly organized structure, which shows similarities to normal hepatic parenchyma. Therefore, they can easily remodel into the lobular structure. Eventually, the regenerated liver is constructed by enlarged hepatic lobules; no new lobules are formed during this process. The foci of the Solt-Farber experimental hepatocarcinogenesis model have identical morphological features; accordingly, they also represent only regenerative, not neoplastic, growth. Conclusion: Progenitor-cell-driven liver regeneration is a well-designed, highly organized tissue reaction, and better comprehension of the architectural events may help us to recognize this process and understand its role in physiological and pathological reactions. (HEPATOLOGY 2012;56:1457-1467 T here are several alternative mechanisms of liver regeneration. 1 Hepatocytes can enter the cell cycle or enlarge, and the consequent compensatory hyperplasia or hypertrophy replaces the lost liver mass. We have demonstrated that new hepatic lobules are not formed during this type of regeneration, but the remaining lobes grow exclusively by the enlargement of preexistent hepatic lobules. 2 If the hepatocytes are compromised, the progenitor cell compartment is activated and the liver regenerates by means of the socalled oval cells in the rat. 3 Oval cells invade the liver parenchyma from the periportal region. They form ductules, which are the extensions of the canals of Hering. 4 The distribution of the differentiating cells can be different, depending on the species and etiology. In human liver, singular intermediate hepatobiliary cells can often be observed in proliferating ductules after extensive necrosis, 5 but small groups of differentiating cells are also described in chronic hepatitis and cirrhosis. 6,7 The 2-acetaminofluorene/partial hepatectomy (AAF-PH) model 8 is one of the most widely applied experiments to study oval cell proliferation and differentiation in rats. We characterized the differentiating progenitor cells in this experimental model. Two alternative patterns of differentiation were observed previously depending on the applied dose of AAF. 9 In the case of a low dose (2.5 mg/kg/day of AAF), differentiation occurred earlier and practically all the oval cells transformed into small, newly formed hepatocytes. If the dose of AAF was higher (5 mg/kg/ day of AAF), differentiation occurred later and involved only a small portion of oval cells. Sharply

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Structural analysis of oval-cell–mediated liver regeneration in rats

et al. 2012

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“…Studies using dye injections into portal and hepatic veins of rat liver suggest that the structural/functional unit of the rat liver is the portal lobule [21]. The difficulty with this model is that according to angioarchitectural studies, a considerably larger portion of the blood supply to rat liver sinusoids originates from the portal venous branch.…”

Section: Discussionmentioning

confidence: 99%

Assessment and histological analysis of the IPRL technique for sequential in situ liver biopsy

et al. 2011

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BackgroundThe isolated perfused rat liver (IPRL) is a technique used in a wide range of liver studies. Typically livers are assessed at treatment end point. Techniques have been described to biopsy liver in the live rat and post-hepatectomy.ResultsThis paper describes a technique for obtaining two full and one partial lobe biopsies from the liver in situ during an IPRL experiment. Our approach of retaining the liver in situ assists in minimising liver capsule damage, and consequent leakage of perfusate, maintains the normal anatomical position of the liver during perfusion and helps to keep the liver warm and moist. Histological results from sequential lobe biopsies in control perfusions show that cytoplasmic vacuolation of hepatocytes is a sign of liver deterioration, and when it occurs it commences as a diffuse pattern which tends to develop a circumscribed, centrilobular pattern as perfusion progresses.ConclusionsLiver lobe biopsies obtained using this method can be used to study temporal effects of drug treatments and are suitable for light and electron microscopy, and biochemical analyses.

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“…28 These studies yielded interesting but very contradictory data, and none was able to visualize Rappaport's liver acinus. Instead, different types of parenchymal units were newly introduced or revisited, such as the portal lobule, 29 so called "cone-shaped primary lobules", 6-8 of which form a classical (central-vein) but secondary lobule according to Matsumoto,12,13 or "primary lobular units" and "liver modules" with differences to, but basically the same organization as the classic (central vein) liver lobule. 10,11 Using a specific experimental model based on the lownumber intrahepatic portal-embolic transplantation of endocrine tissues it took about 50 years to prove the correctness of RappaportЈs acinus model since his first description in 1954.…”

Section: Discussionmentioning

confidence: 99%

Revelation of simple and complex liver acini after portal transplantation of pancreatic islets or thyroid follicles in rats

Dombrowski

Evert

2007

Hepatology

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The microarchitecture of the liver is still not completely understood although various concepts of structural liver organization have been proposed. Among them, Rappaport's liver acinus stands out as one of the most accepted models. The correctness of this model, however, has also been doubted, and its applicability is hampered by the fact that the outlines of the liver acinus are disguised and nobody was ever able to give visual evidence by "unmasking" a simple liver acinus from the surrounding liver tissue. After intraportal transplantation of pancreatic islets or thyroid follicles into diabetic or thyroidectomized rats, respectively, the transplants engraft in small portal tracts and morphologically alter the downstream liver tissue due to excessive hormone secretion. Using a combined approach of perfusion fixation, stereomicroscopy, and light microscopy, we demonstrate in this study that these foci of altered liver tissue represent simple and complex liver acini, exactly as described by Rappaport. We present stereomicroscopical and histological examples of all important cut levels of altered simple and complex liver acini, including their topographical relation to the supplying and draining vessels and to the "central vein" liver lobule. Moreover, by computer-aided reconstruction of serial semi-thin sections, we were able to present the first 3-dimensional images of simple and complex liver acini. Conclusion: Our results prove the correctness of Rappaport's acinus model and confirm the simple liver acinus as the principal microcirculatory unit of the liver. (HEPATOLOGY 2007;45:705-715.)

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The portal lobule in rat liver fibrosis: A re-evaluation of the liver unit

Cited by 33 publications

References 21 publications

Structural analysis of oval-cell–mediated liver regeneration in rats

Structural analysis of oval-cell–mediated liver regeneration in rats

Assessment and histological analysis of the IPRL technique for sequential in situ liver biopsy

Revelation of simple and complex liver acini after portal transplantation of pancreatic islets or thyroid follicles in rats

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