Cross‐species immunohistochemical investigation of the activation of the liver progenitor cell niche in different types of liver disease

Schotanus, Baukje A; Ingh, T.S.G.A.M. van den; Penning, Louis C.; Rothuizen, J.; Roskams, Tania; Spee, Bart

doi:10.1111/j.1478-3231.2009.02024.x

Cited by 35 publications

(51 citation statements)

References 81 publications

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“…28 However, in such cases, this lesion is associated with an active inflammatory process, parenchymal remodeling, and cell proliferation in adjacent hepatocytes, hepatic stellate cells, myofibrocytes, and hepatic progenitor cells. 46 Ductular activity in DPM is quiet with the exception of occasional low-grade cholangitis, and ductular profiles are embedded in abundant extracellular matrix, with ductular profiles extending beyond the margins of portal tracts where they may directly interface with hepatocytes. Bile ductules had no Ki-67 immunoreactivity in the typical cases in this study, confirming the absence of a proliferative ductular reaction.…”

Section: Discussionmentioning

confidence: 99%

Ductal Plate Malformation in the Liver of Boxer Dogs

et al. 2016

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Ductal plate malformations (DPMs) represent developmental biliary disorders with a wide phenotypic spectrum. This study characterizes DPM in 30 Boxer dogs. Median age was 1.5 (range, 0.3-10.0) years, with 12 dogs <1 year. Clinical features included increased serum levels of liver enzymes (28), gastrointestinal signs (16), poor body condition (14), abdominal effusion (9), and hepatic encephalopathy (2). Additional malformations included gallbladder atresia (8), atrophied left liver (2), absent quadrate lobe with leftdisplaced gallbladder (1), portal vasculature atresia (left liver, 1), intrahepatic portosystemic shunt (1), and complex intrahepatic arteriovenous malformation (1). All dogs had portal tracts dimensionally expanded by a moderate-to-severe multiple small bile duct phenotype embedded in abundant extracellular matrix; 80% displayed variable portal-to-portal bridging. Quantitative analysis confirmed significantly increased fibrillar collagen and a 3-fold increased portal tract area relative to 6 Boxer and 10 non-Boxer controls. Biliary phenotype was dominated by tightly formed CK19-positive ductules, typically 10 to 15 mm in diameter, with 3 to >30 profiles per portal tract, reduced luminal apertures, and negative Ki-67 immunoreactivity. CK19-positive biliary epithelium intersected directly with zone 1 hepatocytes as a signature feature when considered with other DPM characteristics. Phenotypic variation included a multiple small bile duct phenotype (all dogs), predominantly thin-walled sacculated ducts (4), well-formed saccular ducts (4), and sacculated segmental, interlobular, and intralobular ducts (Caroli malformation, 2 dogs, one with bridging portal fibrosis). Histologic evidence of portal venous hypoperfusion accompanied increased biliary profiles in every case. We propose that this spectrum of disorders be referred to as DPM with appropriate modifiers to characterize the unique phenotypes.

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Section: Discussionmentioning

confidence: 99%

Ductal Plate Malformation in the Liver of Boxer Dogs

et al. 2016

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“…In this scenario, hepatic progenitor cells (HPCs) become activated and are sufficient to regenerate the biliary and hepatocellular epithelium (7,8). The biology of HPCs is less studied in comparison to analogous progenitor cells in other adult tissues, and markers that delineate the stem versus transit amplifying populations are not clearly defined (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Differentiation of progenitors in the liver: a matter of local choice

Boulter¹,

Lu²,

Forbes³

2013

J. Clin. Invest.

106

104

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The liver is a complex organ that requires multiple rounds of cell fate decision for development and homeostasis throughout the lifetime. During the earliest phases of organogenesis, the liver acquires a separate lineage from the pancreas and the intestine, and subsequently, the liver bud must appropriately differentiate to form metabolic hepatocytes and cholangiocytes for proper hepatic physiology. In addition, throughout life, the liver is bombarded with chemical and pathological insults, which require the activation and correct differentiation of adult progenitor cells. This Review seeks to provide an overview of the complex signaling relationships that allow these tightly regulated processes to occur.

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“…6 In experimental models and various human liver diseases, LPC expand in close proximity to a-smooth muscle actin (aSMA)-positive cells deriving from either sinusoidal hepatic stellate cells (HSC) or portal fibroblasts depending upon the location of the injury in the lobule. 2,7 There are increasing data demonstrating an intimate cross-talk between LPC and aSMA-positive myofibroblasts 3,[8][9][10][11] and several studies in rodent models and human diseases have pointed out a strong relationship between severity of fibrosis and intensity of the ductular reaction. [12][13][14][15] Interactions between LPC and sinusoidal HSC or portal fibroblasts are poorly understood but their activation could occur independently, successively or in tandem through similar stimuli.…”

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confidence: 99%