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Hepatic stem cell

Pavel Sumazin, Yidong Chen, Lisa R Treviño, Stephen F Sarabia, Oliver A Hampton, Kayuri Patel, Toni-Ann Mistretta, Barry Zorman, Patrick Thompson, Andras Heczey, Sarah Comerford, David A Wheeler, Murali Chintagumpala, Rebecka Meyers, Dinesh Rakheja, Milton J Finegold, Gail Tomlinson, D Williams Parsons, Dolores López-Terrada
Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pre-treatment tumors have been molecularly profiled and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pre-treatment HBs at diagnosis. Our analysis of 88 clinically-annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated NFE2L2 activity, high LIN28B, HMGA2, SALL4 and AFP expression, and high coordinated expression of oncofetal proteins and stem cell markers; while low-risk tumors had low LIN28B and let-7 expression, and high HNF1A activity...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ying Liu, Yang Qi, Zhi-Hui Bai, Chen-Xu Ni, Qi-Hui Ren, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Lei Qiu, Jian-Zhong Li, Zhi-Gao He, Jun-Ping Zhang
AIM: Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, which has shown chemopreventive potential against various cancers. In this study, we evaluated the anticancer efficacy of a novel derivative of matrine, (6aS, 10S, 11aR, 11bR, 11cS)-10- methylamino-dodecahydro- 3a,7a-diaza-benzo (de) (MASM), against human hepatocellular carcinoma (HCC) cells and their corresponding sphere cells in vitro and in vivo. METHODS: Human HCC cell lines (Hep3B and Huh7) were treated with MASM...
October 24, 2016: Acta Pharmacologica Sinica
Shanzheng Lu, Ganggang Shi, Xiaoxi Xu, Grace Wang, Xu Lan, Peng Sun, Xiang Li, Baoren Zhang, Xiangying Gu, Thomas E Ichim, Hao Wang
BACKGROUND: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4...
October 22, 2016: Journal of Translational Medicine
Robim M Rodrigues, Olivier Govaere, Tania Roskams, Tamara Vanhaecke, Vera Rogiers, Joery De Kock
This data set is composed of transcriptomics analyses of (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF) and (ii) hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC). Data from primary human hepatocytes was also added to the data set "Open TG-GATEs: a large-scale toxicogenomics database" (Igarashi et al...
June 2016: Data in Brief
Stacey S Huppert, Kathleen M Campbell
PURPOSE OF REVIEW: Although the liver possesses a unique, innate ability to regenerate through mass compensation, transplantation remains the only therapy when damage outpaces regeneration, or liver metabolic capacity is irreversibly impacted. Recent insight from developmental biology has greatly influenced the advancement of alternative options to transplantation in these settings. RECENT FINDINGS: Factors known to direct liver cell specification, expansion, and differentiation have been used to generate hepatocyte-like cells from stem and somatic cells for developing cell therapies...
October 15, 2016: Current Opinion in Organ Transplantation
Lokesh Shahani
Liver failure is a frequent and serious complication that causes morbidity and mortality in haematopoietic stem cell transplantation (HCT) recipients. Liver dysfunction in these patients can be related to infectious causes, most common viral hepatitis. We report a case of disseminated acyclovir-resistant herpes simplex virus (HSV) infection following HCT that led to acute liver failure and death. Although rare, HSV hepatitis leads to high morbidity and mortality and should be considered in the differential diagnosis of HCT recipients with marked elevation of hepatic transaminase...
October 17, 2016: BMJ Case Reports
Masakazu Sugiyama, Tomoharu Yoshizumi, Yoshihiro Yoshida, Yuki Bekki, Yoshihiro Matsumoto, Shohei Yoshiya, Takeo Toshima, Toru Ikegami, Shinji Itoh, Norifumi Harimoto, Shinji Okano, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara
Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome-1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62 and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically-induced liver injury...
October 17, 2016: Journal of Cellular Physiology
Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T Jake Liang
BACKGROUND AND AIMS: One major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells. METHODS: HLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined...
October 13, 2016: Journal of Hepatology
Kana Yanagihara, Yujung Liu, Kei Kanie, Kazuo Takayama, Minako Okamura, Mitsuhi Hirata, Takayuki Fukuda, Mika Suga, Hiroki Nikawa, Hiroyuki Mizuguchi, Ryuji Kato, Miho K Furue
Functional hepatocytes derived from human pluripotent stem cells (hPSCs) have potential as tools for predicting drug-induced hepatotoxicity in the early phases of drug development. However, the propensity of hPSC lines to differentiate into specific lineages is reported to differ. The ability to predict low propensity of hPSCs to differentiate into hepatocytes would facilitate the selection of useful hPSC clones and substantially accelerate development of hPSC-derived hepatocytes for pharmaceutical research...
October 12, 2016: Stem Cells and Development
Christine Lin, Salman R Khetani
Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions...
2016: BioMed Research International
Kensuke Usuki
Treatments of aplastic anemia are comprised of supportive therapy and aplastic anemia-specific therapy aimed at restoring hematopoiesis. Supportive therapies include transfusion, G-CSF, and the administration of iron chelation agents, as well as dealing specifically with individual symptoms. Aplastic anemia-specific treatments given with the aim of achieving hematopoietic recovery include immunosuppressive therapy, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although transplantation provides complete recovery of hematopoiesis (cure), there is a risk of death due to transplant-related complications...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Eucario Leon-Rodriguez, Monica M Rivera-Franco
Busulfan (Bu), an alkylating agent, has been used in pre-transplant conditioning regimens since the 1950s, due to its potent myeloablative effect. Questions have been raised regarding oral or intravenous formulations, although both are known to be associated with serious side effects, including hepatic veno-occlusive disease, and neurotoxicity. The administration of anticonvulsant prophylaxis has become more common during high-dose Bu-based conditioning regimen; however, anticonvulsants can interfere with Bu pharmacokinetics and may have their own side effects, which can affect the outcome of the transplant...
October 8, 2016: International Journal of Hematology
N A Wijetunga, M Pascual, J Tozour, F Delahaye, M Alani, M Adeyeye, A W Wolkoff, A Verma, J M Greally
The predisposition of patients with Hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) involves components of viral infection, inflammation and time. The development of multifocal, genetically distinct tumours is suggestive of a field defect affecting the entire liver. The molecular susceptibility mediating such a field defect is not understood. One potential mediator of long-term cellular reprogramming is heritable (epigenetic) regulation of transcription, exemplified by DNA methylation. We studied epigenetic and transcriptional changes in HCV-infected livers in comparison with control, uninfected livers and HCC, allowing us to identify pre-neoplastic epigenetic and transcriptional events...
October 10, 2016: Oncogene
Tong Li, Ke Jin, Dan-Yan Zhu, Lu Li, Zheng Rong Mao, Bo Wen Wu, Yi Fan Wang, Zong Fu Pan, Lan Juan Li, Chun Sheng Xiang, Kun Kai Su, Yi Jia Lou
The in vitro predictive evaluation of chemical carcinogenicity based on hepatic premalignance has so far not been established. Here, we report a novel approach to investigate the premalignant events triggered by human carcinogen aristolochic acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6 phenotypic characteristics. Hepatocytes expressed STAT3/p-STAT3, c-Myc and Lin28B in parallel. Some of them displayed the dedifferentiation characteristics, such as full of α-fetoprotein granules, increase in size, and nucleocytoplasmic shuttle of Oct4...
October 4, 2016: Oncotarget
Fei Chen, Hao Yao, Minjun Wang, Bing Yu, Qinggui Liu, Jianxiu Li, Zhiying He, Yi-Ping Hu
Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their abilities for self-renewal and bi-potential differentiation. However, the molecular mechanism regulating proliferation and differentiation of iHepSCs is poorly understood. In this study, we provide evidence that the homeodomain transcription factor, Pitx2, is essential to maintain iHepSCs stem cell characteristics. Suppressing Pitx2 expression in iHepSCs by lentivirus mediated specific shRNA markedly reduced the expression of the hepatic stem cell-associated genes (Lgr5, EpCAM, and Sox9) with concomitant inhibition of proliferation by blocking the G1/S phase transition, and these phenotypic changes were reversed upon re-expression of Pitx2...
September 30, 2016: International Journal of Biochemistry & Cell Biology
Raffaella Greco, Lara Crucitti, Maddalena Noviello, Sara Racca, Daniele Mannina, Alessandra Forcina, Francesca Lorentino, Veronica Valtolina, Serena Rolla, Roee Dvir, Mara Morelli, Fabio Giglio, Maria Chiara Barbanti, Maria Teresa Lupo Stanghellini, Chiara Oltolini, Luca Vago, Paolo Scarpellini, Andrea Assanelli, Matteo G Carrabba, Sarah Marktel, Massimo Bernardi, Consuelo Corti, Massimo Clementi, Jacopo Peccatori, Chiara Bonini, Fabio Ciceri
Human herpesvirus 6 (HHV-6) is increasingly recognized as a potentially life-threatening pathogen in allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively evaluated 54 adult patients who developed positivity to HHV-6 after alloSCT. The median time from alloSCT to HHV-6 reactivation was 34 days. HHV-6 was present in plasma samples from 31 patients, in bone marrow (BM) of 9 patients, in bronchoalveolar lavage fluid and liver or gut biopsy specimens from 33 patients, and in cerebrospinal fluid of 7 patients...
September 30, 2016: Biology of Blood and Marrow Transplantation
Charles B Nguyen, Courtney W Houchen, Naushad Ali
Liver diseases are the fourth leading cause of mortality among adults in the United States. Patients with chronic liver diseases such as viral hepatitis, fibrosis, and cirrhosis have significantly higher risks of developing hepatocellular carcinoma (HCC). With a dismal five-year survival rate of 11%, HCC is the third most common cause of cancer-related deaths worldwide. Regardless of the underlying cause, late presentation and a lack of effective therapy are the major impediments for successful treatment of HCC...
September 30, 2016: Experimental Biology and Medicine
Farzaneh Khademi, Jafar Ai, Masoud Soleimani, Javad Verdi, Seyed Mohammad Tavangar, Esmaeil Sadroddiny, Mohammad Massumi, Seyed Mahmoud Hashemi
Liver tissue engineering (TE) is rapidly emerging as an effective technique which combines engineering and biological processes to compensate for the shortage of damaged or destroyed liver tissues. We examined the viability, differentiation, and integration of hepatocyte-like cells on an electrospun polyethersulfone (PES) scaffold, derived from human endometrial stem cells (hEnSCs). Natural polymers were separately grafted on plasma-treated PES nanofibers, that is, collagen, heparan sulfate (HS) and collagen-HS...
September 30, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Yu-Hua Li, Ying Xu, Hua-Mei Wu, Jing Yang, Li-Hong Yang, Wan Yue-Meng
BACKGROUND & AIM: Search for an effective therapy for patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) remains an important issue. This study investigated the efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation in patients with HBV-ACLF. METHODS: 45 consecutive entecavir-treated HBV-ACLF patients were prospectively studied. Among these patients, 11 received both plasma exchange (PE) and a single transplantation of UC-MSCs (group A), while 34 received only PE (group B)...
September 29, 2016: Stem Cell Reviews
Ran-Ran Zhang, Yun-Wen Zheng, Hideki Taniguchi
A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in which the liver has been repopulated with functional human hepatocytes, could serve as a useful tool for investigating human hepatic cell biology, drug metabolism, and other preclinical applications. One of the key factors required for successful transplantation of human hepatocytes into mice is the elimination of the endogenous hepatocytes to prevent competition with the human cells and provide a suitable space and microenvironment for promoting human donor cell expansion and differentiation...
2016: Journal of Visualized Experiments: JoVE
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