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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/28107194/transdifferentiation-of-human-male-germline-stem-cells-to-hepatocytes-in-vivo-via-the-transplantation-under-renal-capsules
#1
Zheng Chen, Minghui Niu, Min Sun, Qingqing Yuan, Chencheng Yao, Jingmei Hou, Hong Wang, Liping Wen, Hongyong Fu, Fan Zhou, Zheng Li, Zuping He
Here we proposed a new concept that human spermatogonial stem cells (SSCs) can transdifferentiate into hepatocytes in vivo. We first established liver injury model of mice by carbon tetrachloride to provide proper environment for human SSC transplantation. Liver mesenchymal cells were isolated from mice and identified phenotypically. Human SSC line was recombined with liver mesenchymal cells, and they were transplanted under renal capsules of nude mice with liver injury. The grafts expressed hepatocyte hallmarks, including ALB, AAT, CK18, and CYP1A2, whereas germ cell and SSC markers VASA and GPR125 were undetected in these cells, implicating that human SSCs were converted to hepatocytes...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105981/cryopreservation-of-hepatocyte-microbeads-for-clinical-transplantation
#2
Suttiruk Jitraruch, Anil Dhawan, Robin D, Celine Filippi, Sharon C, Leanne Glover, Ragai R
Intraperitoneal transplantation of hepatocyte microbeads is an attractive option for the management of acute liver failure. Encapsulation of hepatocytes in alginate microbeads supports their function and prevents immune attack of the cells. Establishment of banked cryopreserved hepatocyte microbeads is important for emergency use. The aim of this study was to develop an optimised protocol for cryopreservation of hepatocyte microbeads for clinical transplantation using modified freezing solutions. Four freezing solutions with potential for clinical application were investigated...
January 20, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#3
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28105130/biological-characterization-of-sheep-kidney-derived-mesenchymal-stem-cells
#4
Meng Ji, Chunyu Bai, Lu Li, Ya'Nan Fan, Caiyun Ma, Xiangchen Li, Weijun Guan
The aim of the present study was to isolate, culture and characterize sheep metanephric mesenchymal stem cells (MMSCs). The MMSCs were isolated from the kidney tissue of six-week-old sheep fetus. This study investigated whether primary MMSCs could be grown for 26 passages and expressed Oct-4, which is involved in the self-renewal of undifferentiated pluripotent stem cells. The MMSCs also expressed the renal lineage marker gene PAX2, and mesenchymal cell marker genes CD44, FN1 and VIM. Expression of these genes was detected using immunofluorescence and reverse transcription-polymerase chain reaction assays...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104124/enhancing-survival-of-human-hepatocytes-by-neonatal-thymectomy-and-partial-hepatectomy-in-micro-miniature-pigs
#5
H C Hsu, S Enosawa, T Yamazaki, S Tohyama, J Fujita, K Fukuda, E Kobayashi
BACKGROUND: With the goal of in vivo cultivation of human hepatocytes that have not been sufficient in full differentiation in vitro, the advantage of neonatal thymectomy was verified on expansion of xenogeneic human hepatocyte in the micro-miniature pig (MMP). METHODS: The thymus was excised immediately after the birth of the MMPs via cesarean section. Newborns were fed by artificial feeding under specific pathogen-free conditions. The thymectomized and nonthymectomized littermates were transplanted with human hepatocytes via a portal vein with or without partial hepatectomy at the MMP adult stage...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104115/pretransplant-serum-hyaluronic-acid-can-be-a-biomarker-as-a-prognostic-predictor-in-adult-to-adult-living-donor-liver-transplantation
#6
S Mizuno, B C Das, Y Iizawa, H Kato, Y Murata, A Tanemura, N Kuriyama, Y Azumi, M Kishiwada, M Usui, H Sakurai, S Isaji
OBJECTIVE: The goal of this study was to evaluate whether pretransplant serum hyaluronic acid (HA) levels can predict outcomes after adult-to-adult living donor liver transplantation (LDLT). METHODS: In study I, 21 patients who underwent LDLT (March 2002-February 2004) were divided into 2 groups: the H-I group (HA ≥500 ng/mL; n = 12) and the L-I group (HA <500 ng/mL; n = 9). The influence of pretransplantation HA levels on short-term surgical outcome was investigated...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28102609/immunogenicity-of-hepatic-differentiated-human-umbilical-cord-mesenchymal-stem-cells-promoted-by-porcine-decellularized-liver-scaffolds
#7
Yi Li, Qiong Wu, Yujia Wang, Li Li, Fei Chen, Yujun Shi, Hong Bu, Ji Bao
Cell-based approaches, including hepatocyte transplantation and tissue-engineered livers, offer promising alternatives and are expected to help support patients with liver diseases until liver transplantation or recovery via regeneration of the damaged liver. However, the success of cell therapies remains dependent on how well the cells are accepted after transplantation and is directly related to their degree of immunogenicity. In this study, hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was induced in the traditional monolayer (2D) culture and newly established three-dimensional (3D) aggregation culture with the porcine decellularized liver scaffold (DLS) system (3D-DLS)...
January 19, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28088007/impairment-of-host-liver-repopulation-by-transplanted-hepatocytes-in-aged-rats-and-the-release-by-short-term-growth-hormone-treatment
#8
Peggy Stock, Maximilian Bielohuby, Martin S Staege, Mei-Ju Hsu, Martin Bidlingmaier, Bruno Christ
Hepatocyte transplantation is an alternative to whole liver transplantation. Yet, efficient liver repopulation by transplanted hepatocytes is low in livers of old animals. This restraint might be because of the poor proliferative capacity of aged donor hepatocytes or the regenerative impairment of the recipient livers. The age-dependent liver repopulation by transplanted wild-type hepatocytes was investigated in juvenile and senescent rats deficient in dipeptidyl-peptidase IV. Repopulation was quantified by flow cytometry and histochemical estimation of dipeptidyl-peptidase IV enzyme activity of donor cells in the negative host liver...
January 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28075444/the-role-of-lncrna-malat1-in-the-regulation-of-hepatocyte-proliferation-during-liver-regeneration
#9
Cuicui Li, Lei Chang, Zhiquan Chen, Zhongzhong Liu, Yanfeng Wang, Qifa Ye
Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) not only regulates tumorigenesis in hepatocellular carcinoma, but also controls cell cycle progression in hematopoietic cells. The present study was designed to investigate the biological role of lncRNA MALAT1 in liver regeneration. We carried out a series of assays during liver regeneration following 2/3 partial hepatectomy in mice...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28062700/intravital-imaging-of-neutrophil-recruitment-reveals-the-efficacy-of-fpr1-blockade-in-hepatic-ischemia-reperfusion-injury
#10
Masaki Honda, Takayuki Takeichi, Shintaro Hashimoto, Daiki Yoshii, Kaori Isono, Shintaro Hayashida, Yuki Ohya, Hidekazu Yamamoto, Yasuhiko Sugawara, Yukihiro Inomata
Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28059835/donor-liver-small-droplet-macrovesicular-steatosis-is-associated-with-increased-risk-for-recipient-allograft-rejection
#11
Won-Tak Choi, Kuang-Yu Jen, Dongliang Wang, Mehdi Tavakol, John P Roberts, Ryan M Gill
Although donor livers with <30% large droplet macrovesicular steatosis (MaS) and/or small droplet MaS (irrespective of percentage) are considered safe to use, this consensus is based on variable definitions of MaS subtypes and/or without a reproducible scoring system. We analyzed 134 donor liver biopsies from allografts transplanted at University of California at San Francisco between 2000 and 2015 to determine whether large and/or small droplet MaS is a risk factor for poor outcomes. Large droplet MaS was defined as a fat droplet occupying greater than one half of an individual hepatocyte, with nuclear displacement, and scored as the percentage of total parenchymal area replaced by large fat droplets on ×40 magnification...
January 4, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28056498/bone-marrow-stem-cell-therapy-partially-ameliorates-pathological-consequences-in-livers-of-mice-expressing-mutant-human-%C3%AE-1-antitrypsin
#12
Prakash Baligar, Veena Kochat, Shailendra K Arindkar, Zaffar Equbal, Snehashish Mukherjee, Swati Patel, Perumal Nagarajan, Sujata Mohanty, Jeffrey H Teckman, Asok Mukhopadhyay
: Alpha1-antitrypsin deficiency (AATD) is a genetic disease, caused by mutation of the AAT gene. Accumulation of mutated AAT protein aggregates in hepatocytes leads to endoplasmic reticulum (ER) stress resulting in impairment of liver functions and in some cases hepatocellular carcinoma, whereas decline of AAT levels in sera is responsible for pulmonary emphysema. In critical cases of liver ailments, the only option for treatment is liver transplantation, whereas AAT replacement therapy is followed in case of emphysema...
January 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28053091/fumarylacetoacetate-hydrolase-knockout-rabbit-model-for-hereditary-tyrosinemia-type-1
#13
Li Li, Quanjun Zhang, Huaqiang Yang, Qingjian Zou, Chengdan Lai, Fei Jiang, Ping Zhao, Zhiwei Luo, Jiayin Yang, Qian Chen, Yan Wang, Philip N Newsome, Jon Frampton, Patrick H Maxwell, Wenjuan Li, Shuhan Chen, Dongye Wang, Tak-Shing Siu, Sidney Tam, Hung-Fat Tse, Baoming Qin, Xichen Bao, Miguel A Esteban, Liangxue Lai
Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedion (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28052626/therapies-in-non-alcoholic-steatohepatitis-nash
#14
REVIEW
Abdul M Oseini, Arun J Sanyal
The hallmark of non-alcoholic fatty liver disease (NAFLD) is excessive fatty accumulation in the hepatocytes, which may be an isolated event (non-alcoholic fatty liver, NAFL) or accompanied by evidence of inflammation and cell injury with or without fibrosis (non-alcoholic steatohepatitis, NASH). NASH, the more aggressive form of NAFLD, may progress to cirrhosis and hepatocellular carcinoma. Since NASH is estimated to overtake hepatitis C virus infection as the leading cause of liver transplantation in the US in the coming decade, and there are no current FDA-approved therapies for this disease, the need to find appropriate therapeutic targets is now more urgent than ever before...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28027971/host-conditioning-and-rejection-monitoring-in-hepatocyte-transplantation-in-humans
#15
Kyle A Soltys, Kentaro Setoyama, Edgar N Tafaleng, Alejandro Soto Gutiérrez, Jason Fong, Ken Fukumitsu, Taichiro Nishikawa, Masaki Nagaya, Rachel Sada, Kimberly Haberman, Roberto Gramignoli, Kenneth Dorko, Veysel Tahan, Alexandra Dreyzin, Kevin Baskin, John J Crowley, Mubina A Quader, Melvin Deutsch, Chethan Ashokkumar, Benjamin L Shneider, Robert H Squires, Sarangarajan Ranganathan, Miguel Reyes-Mugica, Steven F Dobrowolski, George Mazariegos, Rajavel Elango, Donna B Stolz, Stephen C Strom, Gerard Vockley, Jayanta Roy-Chowdhury, Marilia Cascalho, Chandan Guha, Rakesh Sindhi, Jeffrey L Platt, Ira J Fox
BACKGROUND: Hepatocyte transplantation partially corrects genetic disorders and has been associated anecdotally with reversal of acute liver failure. Monitoring for graft function and rejection has been difficult, and has contributed to limited graft survival. METHODS: Preparative hepatic irradiation was examined in non-human primates as a strategy to improve engraftment of donor hepatocytes, and was then applied in human subjects. T-cell immune monitoring was also examined in human subjects to assess adequacy of immunosuppression...
December 24, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28026812/-the-hepatic-differentiation-of-adult-and-fetal-liver-stromal-cells-in-vitro
#16
I V Kholodenko, R V Kholodenko, G V Manukyan, K N Yarygin
The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells...
November 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28012258/functional-defect-of-variants-in-the-adenosine-triphosphate-binding-sites-of-abcb4-and-their-rescue-by-the-cystic-fibrosis-transmembrane-conductance-regulator-potentiator-ivacaftor-vx-770
#17
Jean-Louis Delaunay, Alix Bruneau, Brice Hoffmann, Anne-Marie Durand-Schneider, Véronique Barbu, Emmanuel Jacquemin, Michèle Maurice, Chantal Housset, Isabelle Callebaut, Tounsia Aït-Slimane
: ABCB4 (MDR3) is an adenosine triphosphate (ATP)-binding cassette (ABC) transporter expressed at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene are responsible for several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), a rare disease that can be lethal in the absence of liver transplantation. In this study, we investigated the effect and potential rescue of ABCB4 missense variations that reside in the highly conserved motifs of ABC transporters, involved in ATP binding...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28011329/functional-role-of-ccl5-rantes-for-hcc-progression-during-chronic-liver-disease
#18
Antje Mohs, Nadine Kuttkat, Johanna Reißing, Henning Wolfgang Zimmermann, Roland Sonntag, Amanda Proudfoot, Sameh A Youssef, Alain de Bruin, Francisco Javier Cubero, Christian Trautwein
BACKGROUND & AIMS: During liver inflammation, triggering fibrogenesis and carcinogenesis immune cells play a pivotal role. In the present study we investigated the role of CCL5 in human and in murine models of chronic liver inflammation leading to HCC development. METHODS: CCL5 expression and its receptors were studied in well-defined patients with chronic liver disease (CLD) and in two murine inflammation based HCC models. The role of CCL5 in inflammation, fibrosis, tumor initiation and progression was analyzed in different cell populations of NEMO(Δhepa)/CCL5(-/-) animals and after bone marrow transplantation (BMT)...
December 20, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28009756/regeneration-and-cell-recruitment-in-an-improved-heterotopic-auxiliary-partial-liver-transplantation-model-in-the-rat
#19
Yoshihiro Ono, Angelica Pérez-Gutiérrez, Mladen I Yovchev, Kentaro Matsubara, Shinichiro Yokota, Jorge Guzman-Lepe, Kan Handa, Alexandra Collin de l'Hortet, Angus W Thomson, David A Geller, Hiroshi Yagi, Michael Oertel, Alejandro Soto-Gutierrez
BACKGROUND: Auxiliary partial liver transplantation (APLT) in humans is a therapeutic modality used especially to treat liver failure in children or congenital metabolic disease. Animal models of APLT have helped to explore therapeutic options. Though many groups have suggested improvements, standardizing the surgical procedure has been challenging. Additionally, the question of whether graft livers are reconstituted by recipient-derived cells after transplantation has been controversial...
January 2017: Transplantation
https://www.readbyqxmd.com/read/28003097/hippo-signaling-in-the-liver-regulates-organ-size-cell-fate-and%C3%A2-carcinogenesis
#20
REVIEW
Sachin Patel, Fernando D Camargo, Dean Yimlamai
The Hippo signaling pathway, also known as the Salvador-Warts-Hippo pathway, is a regulator of organ size. The pathway takes its name from the Drosophila protein kinase, Hippo (STK4/MST1 and STK3/MST2 in mammals), which, when inactivated, leads to considerable tissue overgrowth. In mammals, MST1 and MST2 negatively regulate the transcriptional co-activators yes-associated protein 1 and WW domain containing transcription regulator 1 (WWTR1/TAZ), which together regulate expression of genes that control proliferation, survival, and differentiation...
December 19, 2016: Gastroenterology
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