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Hepatic stem cell

Marwa M Abu-Serie
Liver cancer is mainly originated by cancer stem cells (CSCs). Due to difference in pH between normal and tumor cell microenvironments, targeting hepatic CSCs exploiting pH-dependent charge switchable nanoparticles (NPs) is extremely required to limit nonselective toxicity to normal hepatocytes (NHCs) and to completely eliminate the root of cancer origin. In this study, NPs were prepared from cationic chitosan and then coated with anionic albumin namely uncoated and coated NPs, respectively. Both NPs were loaded with diethyldithiocarbamate (DDC) which is an inhibitor of the critical enzyme, aldehyde dehydrogenase (ALDH) 1A1, for CSCs survival...
March 15, 2018: Scientific Reports
Aida Siyahian, Saad Ullah Malik, Adeela Mushtaq, Carol L Howe, Aneela Majeed, Tirdad Zangeneh, Samar Iftikhar, Shahid Habib, Umar Zahid, Irbaz Bin Riaz, Zabih Warraich, Warda Faridi, Faiz Anwer
Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug resistant strains. With the availability of newer antiviral agents like Entecavir, Telbivudine, Adefovir and Tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of seven databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials...
March 12, 2018: Biology of Blood and Marrow Transplantation
Li Li, Bing Chen, Hongbin Yan, Yannan Zhao, Zhongzi Lou, Jianqiu Li, Baoquan Fu, Xingquan Zhu, Donald P McManus, Jianwu Dai, Wanzhong Jia
BACKGROUND: Hepatocyte-based metacestode culture is an attractive method to study alveolar echinococcosis (AE), but it is limited by the relatively short lifespan of cultured hepatocytes in maintaining their normal function. METHODOLOGY/PRINCIPAL FINDINGS: We describe a three-dimensional (3D) hepatic culture system developed from co-cultured hepatocytes and mesenchymal stem cells using a collagen scaffold to study the development of Echinococcus multilocularis larvae...
March 14, 2018: PLoS Neglected Tropical Diseases
Revathi Rajagopal, Marianne Phillips, Nicholas G Gottardo
The initial signs of hepatic sinusoidal obstruction syndrome (HSOS) can be challenging to recognize in children, especially outside the hematopoietic stem cell transplantation setting. To assist clinicians to promptly identify HSOS, the European Society for Blood and Marrow Transplantation has proposed pediatric HSOS diagnostic criteria which emphasize unexplained consumptive and transfusion-refractory thrombocytopenia. To highlight the importance of these "bellwether" early signs of HSOS and the efficacy of pre-emptive treatment with defibrotide, we describe the case of a child with a right 11th rib primitive neuroectodermal tumor who developed HSOS following focal radiotherapy and actinomycin-D treatment...
March 14, 2018: Pediatric Blood & Cancer
Jan Raska, Lucie Ctverackova, Aneta Dydowiczova, Iva Sovadinova, Ludek Blaha, Pavel Babica
HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, α-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed...
March 10, 2018: Toxicology and Applied Pharmacology
Abdel-Rahman N Zekri, Enas Reda El-Sisi, Amira Salah El-Din Youssef, Mahmoud M Kamel, Auhood Nassar, Ola Sayed Ahmed, Mohamed El Kassas, Ahmed Barakat Barakat, Alaa Ismail Abd El-Motaleb, Abeer A Bahnassy
AIM: Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs). METHODS: We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array...
2018: PloS One
Wasco Wruck, James Adjaye
Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs) differentiated into hepatocyte-like cells (HLCs) provide a defined and renewable source of cells for drug screening, toxicology and regenerative medicine. We previously reprogrammed human fetal foreskin fibroblast cells (HFF1) into iPSCs employing an episomal plasmid-based integration-free approach, this iPSC-line and the hESC lines H1 and H9 were used to model hepatogenesis in vitro. Biochemical characterisation confirmed glycogen storage, ICG uptake and release, urea and bile acid production, as well as CYP3A4 activity...
March 13, 2018: Scientific Data
M Joseph John, Amrith Mathew, Sunil Bhat, Anushree Prabhakaran, Biju George, Jacob John
BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are more susceptible to infections from vaccine preventable diseases (VPDs) than the general population. Indian stem cell transplant registry (ISCTR) post-BMT vaccination guidelines were formulated in 2015. The objective of the survey was to assess the compliance to these guidelines among transplant physicians in India. MATERIALS AND METHODS: This is a cross-sectional survey executed as the quantitative research strategy to explore the various aspects of vaccination practices among transplant physicians in India...
March 9, 2018: Vaccine
Youngmin Hwang, MeeiChyn Goh, Mihye Kim, Giyoong Tae
A micropatterned heparin-based hydrogel system that can provide sustained release of multiple growth factors upon one time loading was prepared via photopolymerization and lithography and it was employed as a culture matrix for differentiating hADSCs into hepatic lineage. Mature differentiation of hADSCs into hepatic lineage in terms of gene expression and immunofluorostaining of hepatic markers, and functional characteristics such as glycogen storage ability and production of albumin and urea was observed on the soft hydrogel (∼400 Pa) when the gel elasticity was modulated...
March 3, 2018: Biomaterials
Cong Du, Yuan Feng, Dongbo Qiu, Yan Xu, Mao Pang, Nan Cai, Andy Peng Xiang, Qi Zhang
BACKGROUND: The advent of human-induced pluripotent stem cells holds great promise for producing ample individualized hepatocytes. Although previous efforts have succeeded in generating hepatocytes from human pluripotent stem cells in vitro by viral-based expression of transcription factors and/or addition of growth factors during the differentiation process, the safety issue of viral transduction and high cost of cytokines would hinder the downstream applications. Recently, the use of small molecules has emerged as a powerful tool to induce cell fate transition for their superior stability, safety, cell permeability, and cost-effectiveness...
March 9, 2018: Stem Cell Research & Therapy
Yongting Zhang, Yuwen Li, Lili Zhang, Jun Li, Chuanlong Zhu
Nowadays, orthotopic liver transplantation is considered the most efficient approach to the end stage of chronic hepatic cirrhosis. Because of the limitations of orthotopic liver transplantation, stem cells are an attractive therapeutic option. Mesenchymal stem cells (MSCs) especially show promise as an alternative treatment for hepatic cirrhosis in animal models and during clinical trials. Nevertheless, the homing of transplanted MSCs to the liver occurs in limited numbers. Therefore, we review the strategies for enhancing the homing of MSCs, mainly via the delivery routes, optimizing cell culture conditions, stimulating the target sites, and genetic modification...
March 9, 2018: Stem Cell Research & Therapy
Chao Du, Mingde Jiang, Xiaolong Wei, Jianpin Qin, Hui Xu, Yunxia Wang, Yong Zhang, Dejiang Zhou, Hongli Xue, Shumei Zheng, Weizheng Zeng
It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) alleviated liver fibrosis. We investigated whether BMSCs transfected with human matrix metalloproteinase 1 (BMSCs/MMP1) would improve their therapeutic effect in liver fibrosis induced by carbon tetrachloride (CCl4) in rats. BMSCs were transfected with an adenovirus carrying enhanced green fluorescence protein (GFP) and human MMP1 gene. BMSCs or BMSCs/MMP1 were directly injected into fibrotic rats via the tail vein. GFP-labeled cells appeared in the fibrotic liver after BMSC transplantation...
February 27, 2018: International Journal of Molecular Medicine
Florian Douam, Floriane Fusil, Margot Enguehard, Linda Dib, Francesca Nadalin, Loïc Schwaller, Gabriela Hrebikova, Jimmy Mancip, Laurent Mailly, Roland Montserret, Qiang Ding, Carine Maisse, Emilie Carlot, Ke Xu, Els Verhoeyen, Thomas F Baumert, Alexander Ploss, Alessandra Carbone, François-Loïc Cosset, Dimitri Lavillette
Amino-acid coevolution can be referred to mutational compensatory patterns preserving the function of a protein. Viral envelope glycoproteins, which mediate entry of enveloped viruses into their host cells, are shaped by coevolution signals that confer to viruses the plasticity to evade neutralizing antibodies without altering viral entry mechanisms. The functions and structures of the two envelope glycoproteins of the Hepatitis C Virus (HCV), E1 and E2, are poorly described. Especially, how these two proteins mediate the HCV fusion process between the viral and the cell membrane remains elusive...
March 5, 2018: PLoS Pathogens
Marina Gazdic, Bojana Simovic Markovic, Aleksandar Arsenijevic, Nemanja Jovicic, Aleksandar Acovic, C Randall Harrell, Crissy Fellabaum, Valentin Djonov, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
One of the therapeutic options for the treatment of fulminant hepatitis is re-population of intrahepatic regulatory cells since their pool is significantly reduced during acute liver failure. Although it is known that mesenchymal stem cells (MSCs), which have beneficent effects in the therapy of fulminant hepatitis, may promote expansion of T regulatory cells (Tregs) and B regulatory cells (Bregs), the role of these regulatory cells in MSC-mediated attenuation of acute liver injury is unknown. Herewith, we described the molecular mechanisms involved in the crosstalk between MSCs and liver regulatory cells and analyzed the potential of MSC-based therapy for the expansion of intrahepatic regulatory cells in mouse model of acute liver failure...
March 3, 2018: Liver Transplantation
Fan Li, Yang Liu, Yingyu Cai, Xin Li, Min Bai, Ting Sun, Lianfang Du
This study investigated the impact of ultrasound (US) irradiation on the hepatic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by hepatocyte growth factor (HGF) and the possible mechanisms. We treated hBMSCs, using HGF with and without US irradiation. Cell viability and stem cell surface markers were analyzed. Hepatocyte-like cell markers and functional markers including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen content were analyzed at the time point of day 1, 3 and 5 after treatment...
February 28, 2018: Ultrasound in Medicine & Biology
Brenda C M De Winter, Dennis A Hesselink, Nassim Kamar
Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed and high-income countries. In the majority of cases, HEV causes a self-limiting hepatitis. GT3 and GT4 can be responsible for a chronic hepatitis that can lead to cirrhosis in immunocompromized patients, i.e. solid-organ- and stem-cell-transplant-patients, human immunodeficiency virus-infected patients, and patients receiving chemotherapy or immunotherapy...
February 27, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Viktoriia Starokozhko, Mette Hemmingsen, Layla Larsen, Soumyaranjan Mohanty, Marjolijn Merema, C Rodrigo Pimentel, Anders Wolff, Jenny Emnéus, Anders Aspegren, Geny Groothuis, Martin Dufva
Hepatic differentiation of hiPSCs under flow conditions in a 3D scaffold is expected to be a major step forward for construction of bioartificial livers. The aims of this study were to induce hepatic differentiation of hiPSCs under perfusion conditions and to perform functional comparisons with fresh human precision cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, phase II metabolism, and albumin, urea and bile acid synthesis in the hiPSC derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now...
March 2, 2018: Journal of Tissue Engineering and Regenerative Medicine
Saravana Kumar Kailasam Mani, Ourania Andrisani
Chronic Hepatitis B Virus (HBV) infection is linked to hepatocellular carcinoma (HCC) pathogenesis. Despite the availability of a HBV vaccine, current treatments for HCC are inadequate. Globally, 257 million people are chronic HBV carriers, and children born from HBV-infected mothers become chronic carriers, destined to develop liver cancer. Thus, new therapeutic approaches are needed to target essential pathways involved in HCC pathogenesis. Accumulating evidence supports existence of hepatic cancer stem cells (hCSCs), which contribute to chemotherapy resistance and cancer recurrence after treatment or surgery...
March 2, 2018: Genes
Anja Schöbel, Kathrin Rösch, Eva Herker
Knowledge of activation and interplay between the hepatitis C virus (HCV) and the hosts' innate immunity is essential to understanding the establishment of chronic HCV infection. Human hepatoma cell lines, widely used as HCV cell culture system, display numerous metabolic alterations and a defective innate immunity, hindering the detailed study of virus-host interactions. Here, we analysed the suitability of induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (iHLCs) as a physiologically relevant model to study HCV replication in vitro...
March 1, 2018: Scientific Reports
Kai Liu, Jiyoung Lee, Jing-Hsiung James Ou
Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. In our recent studies, we found that autophagy, or more specifically mitophagy, was required to suppress TP53 and induce the expression of the transcription factor NANOG to maintain hepatic cancer stem cells and promote hepatocarcinogenesis.
2018: Molecular & Cellular Oncology
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