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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/28901189/cryopreservation-of-hepatocyte-microbeads-for-clinical-transplantation
#1
Suttiruk Jitraruch, Anil Dhawan, Robin D Hughes, Celine Filippi, Sharon C Lehec, Leanne Glover, Ragai R Mitry
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 optimized protocol for cryopreservation of hepatocyte microbeads for clinical transplantation using modified freezing solutions. Four freezing solutions with potential for clinical application were investigated...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28893351/hepatic-ischemia-reperfusion-mechanisms-of-tissue-injury-repair-and-regeneration
#2
Takanori Konishi, Alex Lentsch
Hepatic ischemia reperfusion (I/R) injury is a major complication of liver surgery, including liver resection, liver transplantation, and trauma surgery. Much has been learned about the inflammatory injury response induced by I/R, including the cascade of proinflammatory mediators and recruitment of activated leukocytes. In this review, we discuss the complex network of events that culminate in liver injury after I/R, including cellular, protein, and molecular mechanisms. In addition we address the known endogenous regulatory mediators that function to maintain homeostasis and resolve injury...
September 11, 2017: Gene Expression
https://www.readbyqxmd.com/read/28887166/dusp14-protects-against-hepatic-ischemia-reperfusion-injury-via-tak1-suppression
#3
Xiaozhan Wang, Wenzhe Mao, Chun Fang, Song Tian, Xueyong Zhu, Ling Yang, Zan Huang, Hongliang Li
BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (I/R) injury is characterized by severe inflammation and extensive cell death. Multiple signaling pathways, including NF-κB and MAPK/Jnk, play important roles in this process. Identifying the unknown critical regulators of these signaling pathways may provide potential targets for therapeutic application. Dual specific phosphatase 14 (DUSP14) acts as a negative regulator of NF-κB signaling. However, the function of Dusp14 in hepatic I/R injury remains unknown...
September 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28885495/isoglycyrrhizinate-magnesium-enhances-hepatoprotective-effect-of-fk506-on-ischemia-reperfusion-injury-through-hmgb1-inhibition-in-a-rat-model-of-liver-transplantation
#4
Zhang Weichen, Li Feibo, Ye Yufu, Liu Yuanxing, Yu Songfeng, Cen Chao, Chen Xuliang, Zhou Lin, Tang Xiaofeng, Yu Jun, Zheng Shusen
BACKGROUND: Ischemia-reperfusion injury (IRI) after liver transplantation impairs graft function and affects prognosis of recipients. Isoglycyrrhizinate magnesium (Iso) is a hepatoprotective drug usually used after liver injury. In this study, we intended to explore whether Iso alone have protective effect after IRI in a rat model of liver transplantataion. We also aimed to study whether Iso could enhance the hepatoprotective effect of FK506 (tacrolimus) and underlying mechanism. METHODS: Rats after liver transplantation were treated with different concentration of FK506 with or without, Iso or lower-dose FK506 plus Iso...
September 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28870599/hepatocyte-nuclear-factor-4a-improves-hepatic-differentiation-of-immortalized-adult-human-hepatocytes-and-improves-liver-function-and-survival
#5
Hua-Lian Hang, Xin-Yu Liu, Hai-Tian Wang, Ning Xu, Jian-Min Bian, Jian-Jun Zhang, Lei Xia, Qiang Xia
Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH...
September 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28865518/radiation-induced-liver-toxicity
#6
REVIEW
Pablo Munoz-Schuffenegger, Sylvia Ng, Laura A Dawson
The advent of highly conformal radiation therapy (RT) has defined a new role for RT in the treatment of both primary and metastatic liver cancer. Despite major advances in how RT is delivered, radiation-induced liver disease (RILD) remains a concern. Classic RILD, characterized by anicteric ascites and hepatomegaly, is unlikely to occur if treating to doses of ≤30Gy in 2Gy per fraction in patients with baseline Child-Pugh A liver function. On the other hand, nonclassic RILD is a spectrum of liver toxicity, including a general decline in liver function and elevation of liver enzymes...
October 2017: Seminars in Radiation Oncology
https://www.readbyqxmd.com/read/28864074/evaluation-of-antiviral-effect-of-type-i-ii-and-iii-interferons-on-direct-acting-antiviral-resistant-hepatitis-c-virus
#7
Atsushi Hamana, Yuki Takahashi, Takuro Uchida, Makiya Nishikawa, Michio Imamura, Kazuaki Chayama, Yoshinobu Takakura
Treatment of hepatitis C virus (HCV) infection has greatly improved in the last 5 years because of the identification of direct-acting antivirals (DAAs). However, concerns exist regarding the emergence of drug resistance-associated substitutions (RASs). In this study, we evaluated the in vivo antiviral effect of three classes of interferons (IFNs), namely, types I, II, and III IFNs, on DAA-resistant HCVs. IFN-α2, IFN-γ, and IFN-λ1 were selected as typical types I, II, and III IFNs, respectively. Human hepatocyte-transplanted chimeric mice were infected with NS3-D168, NS5A-L31-, and NS5A-Y93-mutated HCVs, and the antiviral effect of IFN-α2, IFN-γ, and IFN-λ1 on these HCV RASs was examined...
August 31, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28855398/targeting-the-vascular-and-perivascular-niches-as-a-regenerative-therapy-for-lung-and-liver-fibrosis
#8
Zhongwei Cao, Tinghong Ye, Yue Sun, Gaili Ji, Koji Shido, Yutian Chen, Lin Luo, Feifei Na, Xiaoyan Li, Zhen Huang, Jane L Ko, Vivek Mittal, Lina Qiao, Chong Chen, Fernando J Martinez, Shahin Rafii, Bi-Sen Ding
The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts establishes "hospitable soil" to foster the incorporation of "seed," in this case, the engraftment of parenchymal cells in injured organs...
August 30, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28815768/micro-vesicles-derived-from-human-wharton-s-jelly-mesenchymal-stromal-cells-mitigate-renal-ischemia-reperfusion-injury-in-rats-after-cardiac-death-renal-transplantation
#9
Xiaoqiang Wu, Tianzhong Yan, Zhiwei Wang, Xuan Wu, Guanghui Cao, Chan Zhang, Xiangyong Tian, Junpeng Wang
The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton-Jelly mesenchymal stromal cells derived micro-vesicles (hWJMSCs-MVs) on renal ischemia-reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24 h, 48 h, 1 and 2 weeks post-transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 levels in the serum...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28807057/inhibitory-effects-of-hnf4%C3%AE-on-migration-maltransformation-of-hepatic-progenitors-hnf4%C3%AE-overexpressing-hepatic-progenitors-for-liver-repopulation
#10
Ping Wang, Min Cong, Tianhui Liu, Hufeng Xu, Lin Wang, Guangyong Sun, Aiting Yang, Dong Zhang, Jian Huang, Yameng Sun, Wenshan Zhao, Hong Ma, Jidong Jia, Hong You
BACKGROUND: Although they are expandable in vitro, hepatic progenitors are immature cells and share many immunomarkers with hepatocellular carcinoma, raising potential concerns regarding maltransformation after transplantation. This study investigated the effects of hepatic nuclear factor (HNF) 4α on the proliferation, migration, and maltransformation of hepatic progenitors and determined the feasibility of using these manipulated cells for transplantation. METHODS: The effects of HNF4α on rat hepatic progenitors (i...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28782153/n-acetylcysteine-and-prednisolone-treatment-improved-serum-biochemistries-in-suspected-flupirtine-cases-of-severe-idiosyncratic-liver-injury
#11
Jürgen Borlak, Florian van Bömmel, Thomas Berg
BACKGROUND & AIMS: The analgesic flupirtine has been linked to cases of severe idiosyncratic drug-induced liver injury (sFILI). We therefore examined whether N-acetylcysteine (NAC) and glucocorticoid therapy is effective in the management of sFILI. METHODS: In a retrospective cohort study efficacy of NAC-infusion and oral prednisolone treatments on liver-function-tests (LFTs) and clinical outcome of 21 sFILI cases was evaluated by comparing it to an external cohort of 30 sFILI cases not receiving the antidote...
August 7, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28767077/gut-liver-axis-derangement-in-non-alcoholic-fatty-liver-disease
#12
REVIEW
Marco Poeta, Luca Pierri, Pietro Vajro
Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis...
August 2, 2017: Children
https://www.readbyqxmd.com/read/28757167/chemical-cocktails-enable-hepatic-reprogramming-of-mouse-fibroblasts-with-a-single-transcription-factor
#13
Ren Guo, Wei Tang, Qianting Yuan, Lijian Hui, Xin Wang, Xin Xie
Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps) using only one transcription factor (TF) (Foxa1, Foxa2, or Foxa3) plus a chemical cocktail...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28751152/human-umbilical-cord-blood-derived-mesenchymal-stromal-cells-and-small-intestinal-submucosa-hydrogel-composite-promotes-combined-radiation-wound-healing-of-mice
#14
Changsun Lee, Sehwan Shim, Hyosun Jang, Hyunwook Myung, Janet Lee, Chang-Hwan Bae, Jae Kyung Myung, Min-Jung Kim, Seung Bum Lee, Won-Suk Jang, Sun-Joo Lee, Hwi-Yool Kim, Seung-Sook Lee, Sunhoo Park
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are a promising agent for treating impaired wound healing, and their therapeutic potential may be enhanced by employing extracellular matrix scaffolds as cell culture scaffolds or transplant cell carriers. Here, we evaluated the effect of human umbilical cord blood-derived (hUCB)-MSCs and a porcine small intestinal submucosa (SIS)-derived extracellular matrix scaffold in a combined radiation-wound mouse model of impaired wound healing...
July 24, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28750687/extracellular-vesicles-from-human-liver-stem-cells-restore-argininosuccinate-synthase-deficiency
#15
Maria Beatriz Herrera Sanchez, Sara Previdi, Stefania Bruno, Valentina Fonsato, Maria Chiara Deregibus, Sharad Kholia, Sara Petrillo, Emanuela Tolosano, Rossana Critelli, Marco Spada, Renato Romagnoli, Mauro Salizzoni, Ciro Tetta, Giovanni Camussi
BACKGROUND: Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that catalyzes the conversion of citrulline and aspartate to argininosuccinate. Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive disorder characterized by neonatal hyperammonemia, elevated citrulline levels, and early neonatal death. Treatment for this disease is currently restricted to liver transplantation; however, due to limited organ availability, substitute therapies are required...
July 27, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28750366/prophylactic-treatment-with-cerium-oxide-nanoparticles-attenuate-hepatic-ischemia-reperfusion-injury-in-sprague-dawley-rats
#16
Nandini D P K Manne, Ravikumar Arvapalli, Vincent A Graffeo, Venkata V K Bandarupalli, Tolou Shokuhfar, Sweetu Patel, Kevin M Rice, Gautam Kumar Ginjupalli, Eric R Blough
BACKGROUND: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury...
July 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28750044/hcv-replication-in-gastrointestinal-mucosa-potential-extra-hepatic-viral-reservoir-and-possible-role-in-hcv-infection-recurrence-after-liver-transplantation
#17
Giovanna Russelli, Paola Pizzillo, Gioacchin Iannolo, Floriana Barbera, Fabio Tuzzolino, Rosa Liotta, Mario Traina, Giovanni Vizzini, Bruno Gridelli, Ester Badami, Pier Giulio Conaldi
PURPOSE: Hepatitis C virus (HCV) predominantly infects hepatocytes, although it is known that receptors for viral entry are distributed on a wide array of target cells. Chronic HCV infection is indeed characterized by multiple non-liver manifestations, suggesting a more complex HCV tropism extended to extrahepatic tissues and remains to be fully elucidated. In this study, we investigated the gastrointestinal mucosa (GIM) as a potential extrahepatic viral replication site and its contribution to HCV recurrence...
2017: PloS One
https://www.readbyqxmd.com/read/28749819/engraftment-and-repopulation-potential-of-late-gestation-fetal-rat-hepatocytes
#18
Joan M Boylan, Heather Francois-Vaughan, Philip A Gruppuso, Jennifer A Sanders
BACKGROUND: The limited availability of donor organs has led to a search for alternatives to liver transplantation to restore liver function and bridge patients to transplantation. We have shown that the proliferation of late gestation (embryonic day 19; ED19) fetal rat hepatocytes is mitogen-independent, and that mechanisms regulating of mRNA translation, cell cycle progression and gene expression differ from those of adult rat hepatocytes. In the present study, we investigated whether E19 fetal hepatocytes can engraft and repopulate an injured adult liver...
July 27, 2017: Transplantation
https://www.readbyqxmd.com/read/28749008/propofol-post-conditioning-alleviates-hepatic-ischaemia-reperfusion-injury-via-brg1-mediated-nrf2-ho-1-transcriptional-activation-in-human-and-mice
#19
Mian Ge, Huixin Chen, Qianqian Zhu, Jun Cai, Chaojin Chen, Dongdong Yuan, Yi Jin, Weifeng Yao, Ziqing Hei
To explore the effects of propofol post-conditioning (PPC) on hepatic ischaemia/reperfusion injury (HIRI) and the potential mechanisms that might be involved in the interaction of Brahma-related gene1(BRG1) and Nuclear-related factor 2(Nrf2). Patients were randomized into PPC(n = 16) and non-PPC(NPC)( n = 21) groups. Propofol(2 mg/kg) was infused within 10 min. of the onset of liver reperfusion during liver transplantation in the PPC group. Liver function tests, as well as Brg1, Nrf2, Heme oxygenase-1(HO-1) and NADPH:quinone oxidoreductase1(NQO1) expression levels were evaluated...
July 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28746468/ischemic-preconditioning-vs-adenosine-vs-prostaglandin-e1-for-protection-against-liver-ischemia-reperfusion-injury
#20
M Radojkovic, M Stojanovic, G Stanojevic, D Radojkovic, J Gligorijevic, I Ilic, N Stojanovic
Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning...
July 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
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