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liver repopulation

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https://www.readbyqxmd.com/read/29774067/estrogen-receptors-orchestrate-cell-growth-and-differentiation-to-facilitate-liver-regeneration
#1
Ta-Lun Kao, Yu-Ping Kuan, Wei-Chung Cheng, Wei-Chun Chang, Long-Bin Jeng, Shuyuan Yeh, Wen-Lung Ma
Background and Aims: Improving liver regeneration (LR) capacity and thereby liver function reserve is a critical bridging strategy for managing liver failure patients. Since estrogen signaling may participate in LR, our aim was to characterize the roles of ERα and ERβ in LR. Methods: LR capacity and estradiol levels following 2/3rd partial hepatectomy (PHx) were compared in ERα-KO or ERβ-KO vs. wildtype mice. The ERα- or ERβ-related transcriptome and interactome were analyzed from regenerating livers, and then bioinformatics was used for pathway discovery and analysis of interactome-transcriptome relationships...
2018: Theranostics
https://www.readbyqxmd.com/read/29764210/curative-ex-vivo-hepatocyte-directed-gene-editing-in-a-mouse-model-of-hereditary-tyrosinemia-type-1
#2
Caitlin VanLith, Rebekah Guthman, Clara T Nicolas, Kari Allen, Zeji Du, Dong Jin Joo, Scott L Nyberg, Joseph B Lillegard, Raymond Daniel Hickey
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH). It has been previously shown that ex vivo hepatocyte-directed gene therapy using an integrating lentiviral vector to replace the defective Fah gene can cure liver disease in small and large animal models of HT1. In this study, we hypothesized that ex vivo hepatocyte-directed gene editing using CRISPR-Cas9 could be used to correct a mouse model of HT1, in which a single point mutation results in loss of FAH function...
May 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29742805/novel-genetic-activation-screening-in-liver-repopulation-and-cancer-now-crispr-than-ever
#3
EDITORIAL
Morgan Preziosi, Satdarshan P Monga
No abstract text is available yet for this article.
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29735529/global-loss-of-leucine-carboxyl-methyltransferase-1-causes-severe-defects-in-fetal-liver-hematopoiesis
#4
Jocelyn A Lee, Zhengqi Wang, Danielle Sambo, Kevin D Bunting, David C Pallas
Leucine Carboxyl Methyltransferase-1 (LCMT-1)3 methylates the carboxy-terminal leucine α-carboxyl group of the catalytic subunits of the protein phosphatase 2A (PP2A) subfamily of protein phosphatases, PP2Ac, PP4c, and PP6c. LCMT-1 differentially regulates the formation and function of a subset of the heterotrimeric complexes that PP2A and PP4 form with their regulatory subunits. Global LCMT-1 knockout causes embryonic lethality in mice, but LCMT-1 function in development is unknown. In the current study, we analyzed the effects of global LCMT-1 loss on embryonic development...
May 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29732274/clinical-hepatocyte-transplantation-what-is-next
#5
James E Squires, Kyle A Soltys, Patrick McKiernan, Robert H Squires, Stephen C Strom, Ira J Fox, Alejandro Soto-Gutierrez
Purpose of review: Significant recent scientific developments have occurred in the field of liver repopulation and regeneration. While techniques to facilitate liver repopulation with donor hepatocytes and different cell sources have been studied extensively in the laboratory, in recent years clinical hepatocyte transplantation (HT) and liver repopulation trials have demonstrated new disease indications and also immunological challenges that will require the incorporation of a fresh look and new experimental approaches...
December 2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29724658/human-hepatocyte-transplantation-corrects-the-inherited-metabolic-liver-disorder-arginase-deficiency-in-mice
#6
Stephanie A K Angarita, Brian Truong, Suhail Khoja, Matthew Nitzahn, Abha K Rajbhandari, Irina Zhuravka, Sergio Duarte, Michael G Lin, Alex K Lam, Stephen D Cederbaum, Gerald S Lipshutz
The transplantation, engraftment, and expansion of primary hepatocytes have the potential to be an effective therapy for metabolic disorders of the liver including those of nitrogen metabolism. To date, such methods for the treatment of urea cycle disorders in murine models has only been minimally explored. Arginase deficiency, an inherited disorder of nitrogen metabolism that presents in the first two years of life, has the potential to be treated by such methods. To explore the potential of this approach, we mated the conditional arginase deficient mouse with a mouse model deficient in fumarylacetoacetate hydrolase (FAH) and with Rag2 and IL2-Rγ mutations to give a selective advantage to transplanted (normal) human hepatocytes...
April 21, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29712758/microrna-33-regulates-the-population-of-peripheral-inflammatory-ly6c-high-monocytes-through-dual-pathways
#7
Osamu Baba, Takahiro Horie, Tetsushi Nakao, Daihiko Hakuno, Yasuhiro Nakashima, Hitoo Nishi, Yasuhide Kuwabara, Masataka Nishiga, Tomohiro Nishino, Yuya Ide, Fumiko Nakazeki, Satoshi Koyama, Masahiro Kimura, Ritsuko Hanada, Masahiro Kawahara, Takeshi Kimura, Koh Ono
MicroRNA (miR)-33 targets ATP-binding cassette transporter A1 (ABCA1), and its deficiency increases serum HDL-cholesterol (HDL-C) and ameliorates atherosclerosis. Although we previously reported that miR-33 deficiency increased peripheral Ly6Chigh monocytes on ApoE-deficient background, the effect of miR-33 on monocyte population is not fully elucidated especially on wild-type (WT) background.We found that Ly6Chigh monocytes in miR-33-/- mice were decreased in peripheral blood and increased in bone marrow (BM)...
April 30, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29708511/prometheus-revisited
#8
Kai-Yuan Chen, Xiling Shen, Anna Mae Diehl
The liver's extraordinary ability to regenerate has been known since the myth of Prometheus, but the mechanisms involved are still being discovered. Various small animal models have been used in this quest. Two of the most popular include partial hepatectomy (PHx), in which two-thirds of the liver mass is surgically removed to evoke a massive, immediate stimulus for regeneration, and prolonged exposure to toxins that kill liver cells more gradually, provoking chronic regenerative activity. In either case, multiple types of cells must interact effectively to repopulate the organ with functional mature hepatocytes and thus assure ultimate restoration of healthy liver structure and function...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29653123/long-noncoding-rna-lnchand2-promotes-liver-repopulation-via-c-met-signaling
#9
Yanying Wang, Pingping Zhu, Jing Wang, Xiaoxiao Zhu, Jianjun Luo, Shu Meng, Jiayi Wu, Buqing Ye, Luyun He, Ying Du, Lei He, Runsheng Chen, Yong Tian, Zusen Fan
BACKGROUND & AIMS: Long noncoding RNAs (lncRNAs) play important roles in various biological processes and regulate gene expression by diverse mechanisms. However, how lncRNAs regulate liver repopulation is unknown. METHODS: Here we identify a divergent lncRNA termed LncHand2 that is highly expressed over liver regeneration after partial hepatectomy (PHx). RESULTS: LncHand2 is constitutively expressed in the nuclei of pericentral hepatocytes in mouse and human livers...
April 10, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29643975/physiological-hypoxia-enhances-stemness-preservation-proliferation-and-bidifferentiation-of-induced-hepatic-stem-cells
#10
Xiaosong Zhi, Jun Xiong, Mengchao Wang, Hongxia Zhang, Gang Huang, Jian Zhao, Xiaoyuan Zi, Yi-Ping Hu
Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their self-renewal and bipotential differentiation properties. However, the efficiency of bidifferentiation and repopulation efficiency of iHepSCs is relatively low. Recent evidence shows that physiological hypoxia, a vital factor within stem cell "niche" microenvironment, plays key roles in regulating tissue stem cell biological behaviors including proliferation and differentiation. In this study, we found that physiological hypoxia (10% O2 ) enhanced the stemness properties and promoted the proliferation ability of iHepSCs by accelerating G1/S transition via p53-p21 signaling pathway...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29620470/study-of-an-outbreak-of-highly-pathogenic-avian-influenza-h5n8-in-commercial-pekin-ducks-anas-platyrhynchos-domesticus-in-california
#11
Simone Stoute, Beate Crossley, H L Shivaprasad
A February 2015 outbreak of highly pathogenic avian influenza (HPAI) H5N8 in a flock of commercial Pekin ducks ( Anas platyrhynchos domesticus) in California was investigated in detail. Approximately 17,349 five-wk-old ducks experienced an increased mortality from a normal of eight birds per day to 24, 18, 24, 33, and 61 birds per day, respectively, in the last 5 days prior to flock depopulation. Clinically, there was decreased water and feed consumption, and approximately 1.0% of the affected flock exhibited neurologic signs...
March 2018: Avian Diseases
https://www.readbyqxmd.com/read/29618815/distributed-hepatocytes-expressing-telomerase-repopulate-the-liver-in-homeostasis-and-injury
#12
Shengda Lin, Elisabete M Nascimento, Chandresh R Gajera, Lu Chen, Patrick Neuhöfer, Alina Garbuzov, Sui Wang, Steven E Artandi
Hepatocytes are replenished gradually during homeostasis and robustly after liver injury1, 2 . In adults, new hepatocytes originate from the existing hepatocyte pool3-8 , but the cellular source of renewing hepatocytes remains unclear. Telomerase is expressed in many stem cell populations, and mutations in telomerase pathway genes have been linked to liver diseases9-11 . Here we identify a subset of hepatocytes that expresses high levels of telomerase and show that this hepatocyte subset repopulates the liver during homeostasis and injury...
April 4, 2018: Nature
https://www.readbyqxmd.com/read/29605076/future-approaches-and-therapeutic-modalities-for-acute-liver-failure
#13
REVIEW
Pavan Patel, Nneoma Okoronkwo, Nikolaos T Pyrsopoulos
The current gold standard for the management of acute liver failure is liver transplantation. However, because of organ shortages, other modalities of therapy are necessary as a possible bridge. This article discusses the current modalities as well as the future management of acute liver failure. Liver assist devices, hepatocyte transplantation, stem cell transplant, organogenesis, and repopulation of decellularized organs are discussed.
May 2018: Clinics in Liver Disease
https://www.readbyqxmd.com/read/29572897/acute-hbv-infection-in-humanized-chimeric-mice-has-multiphasic-viral-kinetics
#14
Yuji Ishida, Tje Lin Chung, Michio Imamura, Nobuhiko Hiraga, Suranjana Sen, Hiroshi Yokomichi, Chise Tateno, Laetitia Canini, Alan S Perelson, Susan L Uprichard, Harel Dahari, Kazuaki Chayama
BACKGROUND: Chimeric uPA/SCID mice reconstituted with humanized livers are useful for studying HBV infection in the absence of an adaptive immune response. However, the detailed characterization of HBV infection kinetics necessary to enable in-depth mechanistic studies in this novel in vivo HBV infection model is lacking. METHODS: To characterize HBV kinetics post-inoculation (p.i.) to steady state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured from 1 minute to 63 days p...
March 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29562778/evidence-of-amniotic-epithelial-cell-differentiation-toward-hepatic-sinusoidal-endothelial-cells
#15
Monica Serra, Michela Marongiu, Antonella Contini, Toshio Miki, Erika Cadoni, Ezio Laconi, Fabio Marongiu
Amniotic epithelial cells (AECs) represent a useful and noncontroversial source for liver-based regenerative medicine, as they can differentiate into hepatocytes upon transplantation into the liver. However, the possibility that AECs can differentiate into other liver cell types, such as hepatic sinusoidal endothelial cells (HSECs), has never been assessed. In order to test this hypothesis, rat- and human-derived AECs (rAECs and hAECs, respectively) were subjected to endothelial cell tube formation assay in vitro...
January 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29517978/trap-seq-identifies-cystine-glutamate-antiporteras-a-driver-of-recovery-from-liver-injury
#16
Amber W Wang, Kirk J Wangensteen, Yue J Wang, Adam M Zahm, Nicholas G Moss, Noam Erez, Klaus H Kaestner
Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We used translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29402311/hepatic-stem-cells-with-self-renewal-and-liver-repopulation-potential-are-harbored-in-cdcp1-positive-subpopulations-of-human-fetal-liver-cells
#17
Ran-Ran Zhang, Yun-Wen Zheng, Bin Li, Yun-Zhong Nie, Yasuharu Ueno, Tomonori Tsuchida, Hideki Taniguchi
BACKGROUND: Mature human hepatocytes are critical in preclinical research and therapy for liver disease, but are difficult to manipulate and expand in vitro. Hepatic stem cells (HpSCs) may be an alternative source of functional hepatocytes for cell therapy and disease modeling. Since these cells play an import role in regenerative medicine, the precise characterization that determines specific markers used to isolate these cells as well as whether they contribute to liver regeneration still remain to be shown...
February 5, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29399275/bioengineered-humanized-livers-as-better-three-dimensional-drug-testing-model-system
#18
Sandeep Kumar Vishwakarma, Avinash Bardia, Chandrakala Lakkireddy, Raju Nagarapu, Md Aejaz Habeeb, Aleem Ahmed Khan
AIM: To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS: Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses...
January 27, 2018: World Journal of Hepatology
https://www.readbyqxmd.com/read/29383183/multi-color-rgb-marking-enables-clonality-assessment-of-liver-tumors-in-a-murine-xenograft-model
#19
Michael Thomaschewski, Kristoffer Riecken, Ludmilla Unrau, Tassilo Volz, Kerstin Cornils, Harald Ittrich, Denise Heim, Henning Wege, Ercan Akgün, Marc Lütgehetmann, Jan Dieckhoff, Michael Köpke, Maura Dandri, Daniel Benten, Boris Fehse
We recently introduced red-green-blue (RGB) marking for clonal cell tracking based on individual color-coding. Here, we applied RGB marking to study clonal development of liver tumors. Immortalized, non-tumorigenic human fetal hepatocytes expressing the human telomerase reverse transcriptase (FH-hTERT) were RGB-marked by simultaneous transduction with lentiviral vectors encoding mCherry, Venus, and Cerulean. Multi-color fluorescence microscopy was used to analyze growth characteristics of RGB-marked FH-hTERT in vitro and in vivo after transplantation into livers of immunodeficient mice with endogenous liver damage (uPA/SCID)...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29352225/a-humanized-mouse-model-of-liver-fibrosis-following-expansion-of-transplanted-hepatic-stellate-cells
#20
Daniel Benten, Johannes Kluwe, Jan W Wirth, Nina D Thiele, Antonia Follenzi, Kuldeep K Bhargava, Christopher J Palestro, Michael Koepke, Reni Tjandra, Tassilo Volz, Marc Lutgehetmann, Sanjeev Gupta
Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice...
January 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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