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Abstract: We analyzed hepatocellular carcinoma (HCC) with progenitor cell features using hepatic stem/progenitor cell marker neural cell adhesion molecule (NCAM). Approximately 8.3% of the operated HCC cases expressed NCAM, and 22.3% of the HCC patients had soluble NCAM levels >1000ng/ml (the “highly soluble” NCAM group). Soluble NCAM status was a significant independent factor predictive of long-term survival in patients with HCC, and high levels of soluble NCAM were significantly related to intrahepatic metastasis. The 140-kDa NCAM isoform was specifically detected in the “highly soluble” NCAM group of HCC patients andits related signals are potential drug targets for NCAM+ HCC. [Copyright &y& Elsevier]

Background & Aims: The liver has high regenerative potential. We attempted to establish a novel culture system for extensive expansion of fetal mouse hepatic stem/progenitor cells and to characterize cultured cells. Methods: Hepatic spheroids collected from 6-day floating cultures were cultured on collagen-coated dishes in serum-free conditions in medium containing growth factors. Cultured cells were mainly characterized by immunocytochemistry and flow cytometry or transplanted into adult mice. Results: Approximately 400 expanding hepatic spheroids were generated from every 1 × 106 fetal liver cells. Subsequently, highly replicative colonies were subcultured with maintaining colony formation on collagen-coated dishes. These colonies consisted of small immature α-fetoprotein-positive cells and hepatocytic and cholangiocytic lineage-committed cells. The immature α-fetoprotein-positive cells could be expanded in a reproducible manner at least 5 × 105-fold (which involved at least 30 passages over >6 months) without losing differentiation potential. Flow cytometric analysis showed that all cultured cells expressed CD49f, but not CD34, Thy-1, c-kit, or CD45. Nearly 15% of the cells expressed Sca-1, and approximately 5%–20% of the cells were side population cells. Both sorted side population cells and Sca-1-positive cells (especially side population cells) produced a large number of α-fetoprotein-positive cells and lineage-committed cells. Expanded cells had bidirectional differentiation potential and improved serum albumin levels in mice with severe liver damage. Conclusions: Long-term extensive expansion of transplantable hepatic stem/progenitor cells was reproducibly achieved in a novel serum-free culture system. Moreover, this culture system yielded side population and Sca-1-positive cell populations that included hepatic stem/progenitor cells with differentiation and proliferation properties. [Copyright &y& Elsevier]

Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs. However, there is a lack of detailed guidance on selecting appropriate animal models for CGT therapies targeting specific pancreatic and liver conditions, such as pancreatitis and chronic liver diseases. In this review, the gastrointestinal committee for the International Society for Cell and Gene Therapy provides a summary of current recommendations for animal species and disease model selection, as outlined by the US Food and Drug Administration, with references to EU EMA and Japan PMDA. We discuss a range of small and large animal models, as well as humanized models, that are suitable for preclinical testing of CGT products aimed at treating pancreatic and liver diseases. For each model, we cover the associated pathophysiology, commonly used metrics for assessing disease status, the pros and limitations of the models, and the relevance of these models to human conditions. We also summarize the use and application of humanized mouse and other animal models in evaluating the safety and efficacy of CGT products. This review aims to provide comprehensive guidance for selecting appropriate animal species and models to help bridge the gap between the preclinical research and clinical trials using CGT therapies for specific pancreatic and liver diseases. [ABSTRACT FROM AUTHOR]

Although hepatitis B virus infection is well-described, the additional risk posed by oral bleeding in individuals with chronic hepatitis B virus infection has not been determined. This study aimed to determine the quantity of hepatitis B virus in the saliva of carriers in Japan, as a means of understanding the potential risk for horizontal transmission. Saliva samples from 48 confirmed hepatitis B virus carriers were included in the analysis. Hepatitis B virus concentrations and the presence of occult blood as periodontal disease were evaluated in each sample. Hepatitis B surface antigen was identified in 46 of the 48 samples (98%), with hepatitis B virus DNA identified in 19 of the 48 saliva samples (40%). Occult blood was detected in 32 (67%) samples with the prevalence increasing as a function of age (r = 0.413; P = 0.003). There was a significantly positive correlation between hepatitis B virus DNA levels in the serum and saliva specimens (r = 0.895; P < 0.001). Occult blood in saliva was detected in most participants. The detection of hepatitis B virus DNA correlated positively with hepatitis B virus in the serum and occult blood in the saliva. Therefore, improved care of periodontal disease among older people is important for preventing horizontal transmission of hepatitis B virus. [ABSTRACT FROM AUTHOR]

Abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an adhesion molecule of the immunoglobulin superfamily, has been characterized as a putative tumor suppressor because it is frequently down-regulated in aggressive types of cancer cells. Recently, however, several studies have shown that CEACAM1 actively contributes to malignant progression or migration in some types of tumor cells, suggesting that the role of CEACAM1 might be diverse among different types of cancer cells. To investigate the functional consequences of CEACAM1 expression in hepatocellular carcinoma, we analyzed the status of CEACAM1 in hepatoma cell lines HLF, PLC/PRF/5, HepG2 and KYN-2. We found that CEACAM1 was only expressed in HepG2 cells, which show a unique property for enhanced anchorage-independent growth. When HepG2 cells were treated with small interfering RNA targeted against CEACAM1, the growth rate in monolayer culture was increased. In contrast, when HepG2 cells were cultured in suspension, inhibition of CEACAM1 expression significantly decreased the growth rate, and the speed of cell–cell attachment was repressed. Hyaluronidase treatment attenuated the growth rate of HepG2 cells in suspension culture, indicating that cell–cell attachment is a requisite for anchorage-independent growth. Our data may reveal the dual role of CEACAM1 on hepatocarcinogenesis, by showing that CEACAM1 acts as a tumor suppressor in HepG2 cells in anchorage-dependent growth conditions, while in anchorage-independent growth conditions, it augments cell proliferation by potentiating the cell–cell attachment. [Copyright &y& Elsevier]