Cytokeratins of the Liver and Intestine Epithelial Cells During Development and Disease

Chougule, Priti; Sumitran–Holgersson, Suchitra

doi:10.5772/33491

Cited by 11 publications

(11 citation statements)

References 93 publications

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“…Interestingly, some A3-positive cells appearing in the surface of the fibrotic lesion also reacted to CK19, which is used as a marker for immature epithelial cells. 26,27 Therefore, A3/CK19-double positive cells are regarded as immature cells with epithelial nature which is under regeneration. It has been considered that bone marrow–derived stem cells may participate in regeneration of damaged intestinal mucosal epithelial cells; the cell population of donor-derived epithelial cells increased in regenerative epithelial cells after bone marrow transplantation; these cells play an important role as rescue cells.…”

Section: Discussionmentioning

confidence: 99%

Participation of Somatic Stem Cells, Recognized by a Unique A3 Antibody, in Mucosal Epithelial Regeneration in Dextran Sulfate Sodium (DSS)–Induced Rat Colonic Lesions

et al. 2020

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A3, generated as a monoclonal antibody against rat malignant fibrous histiocytoma cells, recognizes somatic stem cells in rats. We analyzed the distribution of A3-positive cells in dextran sulfate sodium (DSS)–induced colonic lesions consisting of regenerating mucosa and fibrosis. Male 6-week-old F344 rats were administered 5% DSS in drinking water for 5 to 7 days, and lesions at recovery stage were also examined. In untreated control adult colons, A3-positive cells are localized around the crypts where stem cell niche is formed. Histopathologically, in colons of DSS-administered rats, mucosal atrophy, inflammatory cell infiltration, and fibrosis were observed in the lamina propria; thereafter, mucosal epithelia were desquamated, and crypts were decreased gradually with decrease in surrounding A3-positive cells. At the early recovery stage, crypts showed regeneration with reappearance of A3-positive cells. Interestingly, A3-positive cells aggregated in desquamated mucosa surface of fibrosis. Aggregated A3-positive cells coexpressed with vimentin, Thy-1, and partly CK19 but did not react simultaneously with α-SMA. Likely, aggregated A3-positive cells may be rescue cells with nature of both mesenchymal and epithelial cells to maintain self-renewal after injury in the colon. A3 antibody would become a useful tool to investigate the participation of stem cells in rat colonic lesions.

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Section: Discussionmentioning

confidence: 99%

Participation of Somatic Stem Cells, Recognized by a Unique A3 Antibody, in Mucosal Epithelial Regeneration in Dextran Sulfate Sodium (DSS)–Induced Rat Colonic Lesions

et al. 2020

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“…In this study, HPC activation was evaluated by quantifying the epithelial elements of DR, which are isolated HPCs, RDCs, and IHBCs, with the immunohistochemical detection of CK7 as described previously (Libbrecht and Roskams 2002). CK7 and cytokeratin 19 (CK19) are generally recognized as reliable phenotypic markers for HPCs (Chougule and Sumitran-Holgersson 2012), but the immunohistochemical detection of CK7 is more advantageous for the identification of IHBCs. Our main findings can be summarized as follows: (1) varying degrees of enhanced HPC activation existed before IFN treatment in the HCV patients; (2) HPC activation was ameliorated in the SVR patients following IFN treatment; (3) the normalization of HPC activation was associated with the eradication of HCV by IFN treatment and by reduced hepatic fibrosis following IFN treatment; and (4) HCC was encountered in the non-SVR patients along with a greatly enhanced HPC activation.…”

Section: Discussionmentioning

confidence: 99%

Successful Interferon Therapy Reverses Enhanced Hepatic Progenitor Cell Activation in Patients with Chronic Hepatitis C

Noritake

Kobayashi

Ooba

et al. 2015

Journal of Interferon & Cytokine Research

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The enhanced accumulation of hepatic progenitor cells (HPCs) is related to the risk of progression to hepatocellular carcinoma (HCC). Interferon (IFN) treatment reduces HCC risk in patients with chronic hepatitis C virus (HCV) infection. However, the underlying mechanisms remain unclear. The aim of this study was to examine the effects of IFN treatment on HPC activation in HCV patients. Immunohistochemical detection and computer-assisted quantitative image analyses of cytokeratin 7 (CK7) were performed to evaluate HPC activation in paired pre-and post-treatment liver biopsies from 18 HCV patients with sustained virological response (SVR) to IFN-based therapy and from 23 patients without SVR, as well as normal liver tissues obtained from surgical resection specimens of 10 patients. Pretreatment HCV livers showed increased CK7 immunoreactivity, compared with normal livers (HCV: median, 1.38%; normal: median, 0.69%, P = 0.006). IFN treatment reduced hepatic CK7 immunoreactivity (median, 1.57% pre-IFN vs. 0.69% post-IFN, P = 0.006) in SVR patients, but not in non-SVR patients. The development of HCC following IFN treatment was encountered in 3 non-SVR patients who showed high post-IFN treatment CK7 immunoreactivity (>4%). Successful IFN therapy can reverse enhanced HPC activation in HCV patients, which may contribute to the reduced risk of HCC development in these patients.

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“…We subsequently looked at intermediate filament proteins cytokeratin 18 (CK-18) and cytokeratin 19 (CK-19), which are both expressed at the hepatoblast stage of hepatocyte differentiation. In mature cells, CK-18 marks hepatocytes whereas CK-19 expression is specific to cholangiocytes [ 35 , 36 ]. Median expression of CK-18 was 36.17% for the hESC-derived hepatocytes and 45.25% for the hiPSCs in 3D cultured cells and was significantly different to hESC-derived hepatocytes (1.24%) and hiPSCs (4.17%), respectively in 2D cultured cells (p = 1.948E-18; α = 0.05; two-tailed Kruskal-Wallis test with Dunn-Bonferroni posthoc test).…”

Section: Resultsmentioning

confidence: 99%

Mouse decellularised liver scaffold improves human embryonic and induced pluripotent stem cells differentiation into hepatocyte-like cells

et al. 2017

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Liver transplantation is the definitive treatment of liver failure but donor organ shortage limits its availability. Stem cells are highly expandable and have the potential to differentiate into any specialist cell. Use of patient-derived induced Pluripotent Stem Cells (hiPSCs) has the additional advantage for organ regeneration therapies by removing the need for immunosuppression. We compared hepatocyte differentiation of human embryonic stem cells (hESCs) and hiPSCs in a mouse decellularised liver scaffold (3D) with standard in vitro protocol (2D). Mouse livers were decellularised preserving micro-architecture, blood vessel network and extracellular matrix. hESCs and hiPSCs were primed towards the definitive endoderm. Cells were then seeded either in 3D or 2D cultures and the hepatocyte differentiation was continued. Both hESCs and hiPSCs differentiated more efficiently in 3D than in 2D, with higher and earlier expression of mature hepatocyte marker albumin, lipid and glycogen synthesis associated with a decrease in expression of fetal hepatocyte marker alpha-fetoprotein. Thus we conclude that stem cell hepatocyte differentiation in 3D culture promotes faster cell maturation. This finding suggests that optimised 3D protocols could allow generation of mature liver cells not achieved so far in standard 2D conditions and lead to improvement in cell models of liver disease and regenerative medicine applications.

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Cytokeratins of the Liver and Intestine Epithelial Cells During Development and Disease

Cited by 11 publications

References 93 publications

Participation of Somatic Stem Cells, Recognized by a Unique A3 Antibody, in Mucosal Epithelial Regeneration in Dextran Sulfate Sodium (DSS)–Induced Rat Colonic Lesions

Participation of Somatic Stem Cells, Recognized by a Unique A3 Antibody, in Mucosal Epithelial Regeneration in Dextran Sulfate Sodium (DSS)–Induced Rat Colonic Lesions

Successful Interferon Therapy Reverses Enhanced Hepatic Progenitor Cell Activation in Patients with Chronic Hepatitis C

Mouse decellularised liver scaffold improves human embryonic and induced pluripotent stem cells differentiation into hepatocyte-like cells

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