Hepatic Progenitor Cells in Action

Kaur, Savneet; Siddiqui, Hamda; Bhat, Mohsin H.

doi:10.1016/j.ajpath.2015.06.004

Cited by 49 publications

(27 citation statements)

References 67 publications

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“…Now, these tubules are referred to as ductular reaction and they are thought to represent hepatic progenitor cells [1]. Their closed spatial and functional relationship with myofibroblasts put them in the limelight [2–5], since myofibroblasts are the major source of the deposited collagenous matrix. The correlation between the extent of ductular reaction and fibrosis across a range of liver pathologies raises the question if there is a causal relationship between them [6].…”

Section: Introductionmentioning

confidence: 99%

Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models

et al. 2017

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Background and aimsDuctular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis—ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models.MethodsLiver fibrosis/cirrhosis was induced in wild type and TGFβ overproducing transgenic mice by carbon tetrachloride and thioacetamide administration. The effect of thioacetamide was modulated by treatment with imatinib and erlotinib. The extent of ductular reaction and fibrosis was measured by morphometry following cytokeratin 19 immunofluorescent labeling and Picro Sirius staining respectively. The proliferative activity of hepatocytes and ductular reaction was evaluated by BrdU incorporation. The temporal distribution of the parameters was followed and compared within and between different experimental groups.ResultsThere was a strong significant correlation between the extent of fibrosis and ductular reaction in each experimental group. Although imatinib and erlotinib temporarily decreased fibrosis this effect later disappeared. We could not observe negative correlation between the proliferation of hepatocytes and ductular reaction in any of the investigated models.ConclusionsThe stringent connection between ductular reaction and fibrosis, which cannot be influenced by any of our treatment regimens, suggests that there is a close mutual interaction between them instead of a unidirectional causal relationship. Our results confirm a close connection between DR and fibrogenesis. However, since the two parameters changed together we could not establish a causal relationship and were unable to reveal which was the primary event. The lack of inverse correlation between the proliferation of hepatocytes and ductular reaction questions that ductular reaction can compensate for the failing regenerative activity of hepatocytes. No evidences support the persistent antifibrotic property of imatinib or erlotinib.

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Section: Introductionmentioning

confidence: 99%

Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models

et al. 2017

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“…HPCs are thought to reside in the canals of Hering and can be activated and contribute to liver self-renewal and repair in response to liver injury by proliferating and differentiating towards both hepatocytes and biliary epithelial cells [ 13 ]. HPCs play an important role in the development and prognosis of the liver cancer [ 14 – 18 ]. There are a great number of studies revealing that HPCs are one probable origin of liver cancer.…”

Section: Case Presentationmentioning

confidence: 99%

Double primary hepatic cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) originating from hepatic progenitor cell: a case report and review of the literature

Yuan

Huang

et al. 2016

World J Surg Onc

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BackgroundSynchronous development of primary hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in different sites of the liver have rarely been reported before. The purpose of this study is to investigate the clinicopathological characteristics of synchronous double cancer of HCC and ICC.Case presentationA 56-year-old Chinese man without obvious liver cirrhosis was preoperation diagnosed with multiple HCC in segments VI (SVI) and VII (SVII) by the abdominal computed tomography (CT) and contrast-enhanced ultrasonography (CEUS). We performed hepatic resection of both segments. The tumors in SVI and SVII were pathologically diagnosed as ICC and HCC, respectively. Immunohistochemically, the HCC in SVII was positive for HepPar-1 and negative for CK19, while the ICC in SVI tumor was positive for CK19 and negative for HepPar-1. Interestingly, the immunohistochemical results also showed that the classic hepatic progenitor cell (HPCs) markers CD34 and CD117 were both positive of the two tumors. The patient still survived and at a 1-year follow-up did not show evidence of metastasis or new recurrent lesions. We speculate that the two masses may have originated from HPCs based on the findings of this patient.ConclusionsSynchronous development of HCC and ICC is very rare with unique clinical and pathological features. The correct preoperative diagnosis of double hepatic cancer of HCC and ICC is difficult. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were both the independent risk factor to the development of double liver cancer. Hepatic resection is the preferred and most effective treatment choice. The prognosis of synchronous occurrence of double hepatic cancer was poorer than for either HCC or ICC, and the origin of it needs further study.

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“…A variety of cells are thought to contribute to the production of ECM during biliary fibrosis, including hepatic stellate cells (HSCs), hepatic progenitor cells, periportal/portal fibroblasts and other mesenchymal cells via type 2 EMT 3, 13–15 . However, the activated HSCs with high expressed α-smooth muscle actin (α-SMA) are considered as the most potent effective cells that differentiate into ECM-producing myofibroblasts 16 .…”

Section: Introductionmentioning

confidence: 99%

The roles of Toll-like receptor 4 in the pathogenesis of pathogen-associated biliary fibrosis caused by Clonorchis sinensis

Yan

Fan

et al. 2017

Sci Rep

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Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice. The results showed that the levels of collagen depositions, α-SMA and hydroxyproline (Hyp) contents in TLR4mut mice infected by C. sinensis were significantly lower than in those of TLR4wild ones. Furthermore, we found that the activation of TGF-β signaling was impaired in the TLR4mut mice, compared with wild mice when they were challenged to the same dose of C. sinensis metacercariae. Moreover, the mice with TLR4 mutation showed a decreased activation of hepatic stellate cells indicated by the expression of α-SMA, when compared with TLR4wild mice. These data demonstrate that TLR4 contributes to PABF caused by C. sinensis and TLR4 signaling may be a potential medical target for treatment of PABF.

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Hepatic Progenitor Cells in Action

Cited by 49 publications

References 67 publications

Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models

Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models

Double primary hepatic cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) originating from hepatic progenitor cell: a case report and review of the literature

The roles of Toll-like receptor 4 in the pathogenesis of pathogen-associated biliary fibrosis caused by Clonorchis sinensis

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