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Liver progenitor

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https://www.readbyqxmd.com/read/28729654/cryopreservation-protocol-for-human-biliary-tree-stem-progenitors-hepatic-and-pancreatic-precursors
#1
Lorenzo Nevi, Vincenzo Cardinale, Guido Carpino, Daniele Costantini, Sabina Di Matteo, Alfredo Cantafora, Fabio Melandro, Roberto Brunelli, Carlo Bastianelli, Camilla Aliberti, Marco Monti, Daniela Bosco, Pasquale Bartolomeo Berloco, Pierluigi Benedetti Panici, Lola Reid, Eugenio Gaudio, Domenico Alvaro
Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729432/tropomodulin1-controls-erythroblast-enucleation-via-regulation-of-f-actin-in-the-enucleosome
#2
Roberta B Nowak, Julien Papoin, David S Gokhin, Carla Casu, Stefano Rivella, Jeffrey M Lipton, Lionel Blanc, Velia M Fowler
Biogenesis of mammalian red blood cells requires nuclear expulsion by orthochromatic erythoblasts late in terminal differentiation (enucleation), but the mechanism is largely unexplained. Here, we employed high resolution confocal microscopy to analyze nuclear morphology and F-actin rearrangements during the initiation, progression and completion of mouse and human erythroblast enucleation in vivo Mouse erythroblast nuclei acquire a dumbbell-shaped morphology during enucleation, while human bone marrow erythroblast nuclei unexpectedly retain their spherical morphology...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28716722/dynamics-of-proliferative-and-quiescent-stem-cells-in-liver-homeostasis-and-injury
#3
Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M A Verstegen, Marcel J C Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk Ten Berge, Dave Sprengers, Herold J Metselaar, Luc J W van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P Peppelenbosch, Qiuwei Pan
BACKGROUND & AIMS: Adult liver stem cells are usually maintained in a quiescent/slow cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. METHODS: We studied LGR5-positive stem cells using diphtheria toxin receptor (DTR) and green fluorescent protein (GFP) knock-in mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28714104/chronic-inflammation-elicited-liver-progenitor-cell-conversion-to-liver-cancer-stem-cell-with-clinical-significance
#4
Xiao-Feng Li, Cheng Chen, Dai-Min Xiang, Le Qu, Wen Sun, Xin-Yuan Lu, Teng-Fei Zhou, Shu-Zhen Chen, Bei-Fang Ning, Zhuo Cheng, Ming-Yang Xia, Wei-Feng Shen, Wen Yang, Wen Wen, Terence Kin Wah Lee, Wen-Ming Cong, Hong-Yang Wang, Jin Ding
The substantial heterogeneity and hierarchical organization in liver cancer supports the theory of liver cancer stem cell (LCSC). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in NOD/SCID mice, suggesting the malignant transformation of LPC toward LCSC...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28709146/liver-cancers-with-stem-progenitor-cell-features-a-rare-chemotherapy-sensitive-malignancy
#5
Bruno Christian Köhler, Nina Waldburger, Kai Schlamp, Dirk Jäger, Karl Heinz Weiss, Henning Schulze-Bergkamen, Peter Schirmacher, Christoph Springfeld
Primary liver tumors are a heterogeneous group of malignancies. Besides classical hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), combined and intermediate forms of liver cancer exist and can express stem-cell markers like nuclear cell adhesion molecule (NCAM-1/CD56), c-kit (CD117) or epithelial cell adhesion molecule (EpCAM) together with high proliferative activity. Liver tumors with progenitor-cell features are associated with an unfavorable prognosis, but the phenotype has not resulted in therapeutic consequences so far...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706416/implication-of-the-hedgehog-pathway-in-hepatocellular-carcinoma
#6
REVIEW
Carminia Maria Della Corte, Giuseppe Viscardi, Federica Papaccio, Giovanna Esposito, Giulia Martini, Davide Ciardiello, Erika Martinelli, Fortunato Ciardiello, Floriana Morgillo
The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma (HCC) is poor because there are few treatment options. Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis, proliferation and progression of HCC. Among all of the pathways that are involved in the development of HCC, Hedgehog (HH) signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28702321/a-high-content-small-molecule-screen-identifies-novel-inducers-of-definitive-endoderm
#7
Alexander Korostylev, Pallavi U Mahaddalkar, Oliver Keminer, Kamyar Hadian, Kenji Schorpp, Philip Gribbon, Heiko Lickert
OBJECTIVES: Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can generate any given cell type in the human body. One challenge for cell-replacement therapy is the efficient differentiation and expansion of large quantities of progenitor cells from pluripotent stem cells produced under good manufacturing practice (GMP). FOXA2 and SOX17 double positive definitive endoderm (DE) progenitor cells can give rise to all endoderm-derived cell types in the thymus, thyroid, lung, pancreas, liver, and gastrointestinal tract...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28700372/immunohistochemical-demonstration-of-parvovirus-b19-viral-protein-2-in-periflexural-exanthema-in-an-adult-supporting-antibody-dependent-enhancement-as-means-of-endothelial-uptake-of-the-virus
#8
Carlos Santonja, Úrsula Pielasinski, Jorge Polo, Heinz Kutzner, Luis Requena
Human parvovirus B19 (B19V) causes a number of skin exanthemas and has been related to both cutaneous and systemic diseases. Tropism of the virus for the rapidly proliferating erythroid progenitor cells in the bone marrow and fetal liver explains the pathogenesis of anemia and fetal hydrops. The cutaneous lesions of erythema infectiosum and other B19V-related exanthemas have been attributed to the deposition of immune complexes in the skin. We report on the immunohistochemical detection of B19V protein in the cytoplasm of dermal endothelial cells in a case of periflexural exanthema in a 28-year-old woman...
July 6, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28694332/the-ets2-repressor-factor-erf-is-required-for-effective-primitive-and-definitive-hematopoiesis
#9
Ioanna Peraki, James Palis, George Mavrothalassitis
Erf is a ubiquitously expressed ets-DNA-binding containing transcriptional repressor. Erf haploinsufficiency causes craniosynostosis in human and mice, while its absence in mice leads to failed chorioallantoic fusion and death at E10.5. In this study, we show that Erf is required in all three waves of embryonic hematopoiesis. Mice lacking Erf in embryo proper exhibited severe anemia and died around embryonic day (E) 14.5. Erf epiblast specific knockout embryos had reduced numbers of circulating blood cells from E9...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28688656/notch-signaling-promotes-ductular-reactions-in-biliary-atresia
#10
Jessica A Zagory, William Dietz, Alex Park, Michael Fenlon, Jiabo Xu, Sarah Utley, Nirmala Mavila, Kasper S Wang
BACKGROUND: Biliary atresia (BA) is a congenital, progressive, fibro-obliterative disease of the extrahepatic biliary tree and the most common cause of end-stage liver disease in children. BA is characterized by extensive intrahepatic proliferating ductular reactions that may contribute to biliary fibrosis. Lineage tracing during experimental cholestasis indicates that cells within ductular reactions derive from PROM1-expressing hepatic progenitor cells. Given the role of Notch signaling in normal biliary development, we hypothesize that activated Notch signaling promotes the formation of ductular reactions in BA...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28684878/hepatocyte-nuclear-factor-1beta-enhances-the-stemness-of-hepatocellular-carcinoma-cells-through-activation-of-the-notch-pathway
#11
Jing-Ni Zhu, Lu Jiang, Jing-Hua Jiang, Xue Yang, Xiao-Yong Li, Jian-Xin Zeng, Rong-Yu Shi, Yang Shi, Xiao-Rong Pan, Zhi-Peng Han, Li-Xin Wei
Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684664/mesenchymal-stem-stromal-cell-derived-extracellular-vesicles-and-their-potential-as-novel-immunomodulatory-therapeutic-agents
#12
REVIEW
Verena Börger, Michel Bremer, Rita Ferrer-Tur, Lena Gockeln, Oumaima Stambouli, Amina Becic, Bernd Giebel
Extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as mediators of a newly-discovered intercellular communication system. They are essential signaling mediators in various physiological and pathophysiological processes. Depending on their origin, they fulfill different functions. EVs of mesenchymal stem/stromal cells (MSCs) have been found to promote comparable therapeutic activities as MSCs themselves. In a variety of in vivo models, it has been observed that they suppress pro-inflammatory processes and reduce oxidative stress and fibrosis...
July 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28684339/-identification-isolation-quantification-and-systems-approach-towards-cd34-a-biomarker-present-in-the-progenitor-stem-cells-from-diverse-lineages
#13
P Sudheer Shenoy, Bipasha Bose
Mesenchymal stem cells (MSCs) constitute the diverse progenitor populations in almost every tissue and are of immense importance in the field of regenerative medicine. CD34 is a cell surface glycoprotein identified first as a marker for the MSCs of hematopoietic origin. CD34 is now known to be expressed in cells of diverse lineages (tissues of non-hematopoietic origin) such as ectoderm, mesoderm and endoderm and is considered as a general marker for progenitor cells. Here, we present detailed protocols to obtain pure populations of MSCs from three diverse lineages such as skeletal muscle, skin, and liver from mouse tissues...
July 3, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28682508/bone-marrow-endothelial-progenitor-cells-activate-hepatic-stellate-cells-and-aggravate-carbon-tetrachloride-induced-liver-fibrosis-in-mice-via-paracrine-factors
#14
Manali Garg, Savneet Kaur, Arpita Banik, Vikash Kumar, Archana Rastogi, Shiv K Sarin, Asok Mukhopadhyay, Nirupma Trehanpati
OBJECTIVES: Bone marrow derived endothelial progenitor cells (BM-EPCs) are increased in chronic liver disease (CLD). Their role in hepatic fibrosis and regeneration remains an area of intense studies. We investigated the migration and secretory functions of BM-EPCs in fibrotic mice liver. MATERIALS AND METHODS: Bone marrow cells from C57BL6-GFP mice were transplanted into the femur of irradiated C57BL6 mice, followed by CCl4 doses for 8 weeks, to develop hepatic fibrosis (n = 36)...
July 6, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28681484/a-single-cell-transcriptomic-analysis-reveals-precise-pathways-and-regulatory-mechanisms-underlying-hepatoblast-differentiation
#15
Li Yang, Wei-Hua Wang, Wei-Lin Qiu, Zhen Guo, Erfei Bi, Cheng-Ran Xu
How the bi-potential hepatoblasts differentiate into hepatocytes and cholangiocytes remains unclear. Here, using single-cell transcriptomic analysis of hepatoblasts, hepatocytes, and cholangiocytes sorted from E10.5 to E17.5 mouse embryos, we found that hepatoblast-to-hepatocyte differentiation occurred gradually followed a linear default pathway. As more cells became fully differentiated hepatocytes, the number of proliferating cells decreased. Surprisingly, the proliferating and quiescent hepatoblasts exhibited homogeneous differentiation states at a given developmental stage...
July 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28677529/generation-and-characterization-of-a-human-ipsc-cell-line-expressing-inducible-cas9-in-the-safe-harbor-aavs1-locus
#16
Julio Castaño, Clara Bueno, Senda Jiménez-Delgado, Heleia Roca-Ho, Mario F Fraga, Agustín F Fernandez, Mahito Nakanishi, Raúl Torres-Ruiz, Sandra Rodríguez-Perales, Pablo Menéndez
We report the generation-characterization of a fetal liver (FL) B-cell progenitor (BCP)-derived human induced pluripotent stem cell (hiPSC) line CRISPR/Cas9-edited to carry/express a single copy of doxycycline-inducible Cas9 gene in the "safe locus" AAVS1 (iCas9-FL-BCP-hiPSC). Gene-edited iPSCs remained pluripotent after CRISPR/Cas9 genome-edition. Correct genomic integration of a unique copy of Cas9 was confirmed by PCR and Southern blot. Cas9 was robustly and specifically expressed on doxycycline exposure...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28671671/wnt-%C3%AE-catenin-activation-and-macrophage-induction-during-liver-cancer-development-following-steatosis
#17
A Debebe, V Medina, C-Y Chen, I M Mahajan, C Jia, D Fu, L He, N Zeng, B W Stiles, C-L Chen, M Wang, K-R Aggarwal, Z Peng, J Huang, J Chen, M Li, T Dong, S Atkins, Z Borok, W Yuan, K Machida, C Ju, M Kahn, D Johnson, B L Stiles
Obesity confers an independent risk for carcinogenesis. In the liver, steatosis often proceeds cancer formation; however, the mechanisms by which steatosis promotes carcinogenesis is unknown. We hypothesize that steatosis alters the microenvironment to promote proliferation of tumor initiating cells (TICs) and carcinogenesis. We used several liver cancer models to address the mechanisms underlying the role of obesity in cancer and verified these findings in patient populations. Using bioinformatics analysis and verified by biochemical assays, we identified that hepatosteatosis resulting from either Pten deletion or transgenic expression of HCV core/NS5A proteins, promotes the activation of Wnt/β-catenin...
July 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28669772/naoxintong-inhibits-myocardial-infarction-injury-by-vegf-enos-signaling-mediated-neovascularization
#18
Hong Wang, Lizhen Qiu, Yake Ma, Lusha Zhang, Lu Chen, Chunxiao Li, Xiao Geng, Xingyu You, Xiumei Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Naoxintong capsules (NXT), a traditional Chinese Medical preparation, are widely used for treatment of cardiovascular diseases, while the mechanism is still unclear. MATERIALS AND METHODS: Myocardial infarction (MI) was induced by ligation of the left coronary artery in mice. Echocardiographic measurements were performed to do physiological assessments of left ventricle (LV) function. Histological and immunohistochemical staining was used to determine infarct size, capillary density, tissue endothelial nitric oxide synthase (eNOS) expression...
June 29, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28665890/the-impact-of-liver-graft-injury-on-cancer-recurrence-posttransplantation
#19
Chang-Xian Li, Kwan Man, Chung-Mau Lo
Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma (HCC). However, cancer recurrence, posttransplantation, remains to be the critical issue which affects the long-term outcome of HCC recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute phase liver graft injury is a result of hepatic ischemia reperfusion (I/R) injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation...
June 29, 2017: Transplantation
https://www.readbyqxmd.com/read/28664876/scaling-up-of-a-heparg-progenitor-cell-based-bioartificial-liver-optimization-for-clinical-application-and-transport
#20
Martien van Wenum, Philipp Treskes, Chung-Yin Tang, Esmee J Coppens, Koen Jansen, Erik J Hendriks, Sandrine Camus, Thomas M van Gulik, Robert A F M Chamuleau, Ruurdtje Hoekstra
A new generation of bioartificial livers, based on differentiated proliferative hepatocyte sources, has been developed. Several practicable and regulatory demands have to be addressed before these can be clinically evaluated. We identified three main hurdles: (1) expansion and preservation of the biocomponent, (2) development of scaled-up culture conditions and (3) transport of the device to the bedside. In this study we address these three issues for the HepaRG-progenitor cell line-loaded AMC-Bioartificial Liver...
June 30, 2017: Biofabrication
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