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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#1
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27906439/in-vitro-neural-differentiation-of-bone-marrow-stromal-cells-induced-by-hepatocyte-growth-factor-and-glial-cell-derived-neurotrophic-factor
#2
Q Ma, M Cai, J-W Shang, J Yang, X-Y Gu, W-B Liu, Q Yang
OBJECTIVE: Bone marrow stromal cells (BMSCs) have great potential for cell-based transplantation therapy in treating neurological disease. However, the best combination of various trophic factors to produce full neural differentiation of BMSCs was still unclear. In our study, we aimed to investigate the neural differentiation capacity of rat BMSCs induced by growth factors including hepatocyte growth factor (HGF) and glial cell-derived neurotrophic factor (GDNF). MATERIALS AND METHODS:   Cell counting kit-8 (CCK-8) assay, BrdU cell proliferation assay and flow cytometry were implemented to evaluate whether GDNF and HGF had positive effects on the proliferation of BMSCs...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27898091/restoring-ureagenesis-in-hepatocytes-by-crispr-cas9-mediated-genomic-addition-to-arginase-deficient-induced-pluripotent-stem-cells
#3
Patrick C Lee, Brian Truong, Agustin Vega-Crespo, W Blake Gilmore, Kip Hermann, Stephanie Ak Angarita, Jonathan K Tang, Katherine M Chang, Austin E Wininger, Alex K Lam, Benjamen E Schoenberg, Stephen D Cederbaum, April D Pyle, James A Byrne, Gerald S Lipshutz
Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies...
November 29, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27882135/protective-effect-of-enos-overexpression-against-ischemia-reperfusion-injury-in-small-for-size-liver-transplantation
#4
Bo Zhang, Qiu-Hua Liu, Cui-Jie Zhou, Ming-Zheng Hu, Hai-Xin Qian
Ischemia/reperfusion (I/R) injury can occur during small-for-size liver transplantation, resulting in delayed graft function and decreased long-term graft survival. The aim of the present study was to evaluate the effects of genetic overexpression of endothelial nitric oxide synthase (eNOS) in protecting hepatocytes against I/R injury in a rat model of small-for-size liver transplantation. L02 liver cells were transfected with the eNOS gene using an adenovirus (Ad-eNOS). eNOS expression was detected using quantitative polymerase chain reaction and western blot analysis...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27874233/induction-of-hepatocyte-like-cells-from-human-umbilical-cord-derived-mesenchymal-stem-cells-by-defined-micrornas
#5
Xia Zhou, Lina Cui, Xinmin Zhou, Qiong Yang, Lu Wang, Guanya Guo, Yu Hou, Weile Cai, Zheyi Han, Yongquan Shi, Ying Han
Generating functional hepatocyte-like cells (HLCs) from mesenchymal stem cells (MSCs) is of great urgency for bio-artificial liver support system (BALSS). Previously, we obtained HLCs from human umbilical cord-derived MSCs by overexpressing seven microRNAs (HLC-7) and characterized their liver functions in vitro and in vivo. Here, we aimed to screen out the optimal miRNA candidates for hepatic differentiation. We sequentially removed individual miRNAs from the pool and examined the effect of transfection with remainder using RT-PCR, periodic acid-Schiff (PAS) staining and low-density lipoprotein (LDL) uptake assays and by assessing their function in liver injury models...
November 22, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27862079/discarded-livers-find-a-new-life-engineered-liver-grafts-using-hepatocytes-recovered-from-marginal-livers
#6
Basak E Uygun, Maria-Louisa Izamis, Maria Jaramillo, Yibin Chen, Gavrielle Price, Sinan Ozer, Martin L Yarmush
Treatment for end-stage liver failure is restricted by the critical shortage of donor organs; about 4000 people die in the USA while waiting for a transplantable organ. This situation has been a major driving force behind the rise of tissue engineering to build artificial tissues/organs. Recent advancements in creating transplantable liver grafts using decellularized liver scaffolds bring the field closer to clinical translation. However, a source of readily available and highly functional adult hepatocytes in adequate numbers for regenerative liver therapies still remains unclear...
November 8, 2016: Artificial Organs
https://www.readbyqxmd.com/read/27830562/hepatocyte-transplantation-in-children
#7
Louise Coppin, Etienne Sokal, Xavier Stephenne
The liver has an important function in the human body and plays a crucial role in its metabolism. Orthotopic liver transplantation (OLT) is the gold standard treatment for patients presenting liver failure or end stage liver diseases, and is also applied for liver based intractable metabolic disorders. Due to organ shortage, invasive surgery and persistent mortality/morbidity, other treatments have to be explored. Amongst these, hepatocyte transplantation is an attractive alternative and has shown promising results in the treatment of miscellaneous metabolic disorders...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830559/microencapsulation-of-hepatocytes-and-mesenchymal-stem-cells-for-therapeutic-applications
#8
Raphael P H Meier, Elisa Montanari, Philippe Morel, Joël Pimenta, Henk-Jan Schuurman, Christine Wandrey, Sandrine Gerber-Lemaire, Redouan Mahou, Leo H Bühler
Encapsulated hepatocyte transplantation and encapsulated mesenchymal stem cell transplantation are newly developed potential treatments for acute and chronic liver diseases, respectively. Cells are microencapsulated in biocompatible semipermeable alginate-based hydrogels. Microspheres protect cells against antibodies and immune cells, while allowing nutrients, small/medium size proteins and drugs to diffuse inside and outside the polymer matrix. Microencapsulated cells are assessed in vitro and designed for experimental transplantation and for future clinical applications...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830558/isolation-of-hepatocytes-and-stellate-cells-from-a-single-piece-of-human-liver
#9
Serene M L Lee, Tobias S Schiergens, Maresa Demmel, Reinhard M K Thasler, Wolfgang E Thasler
Co-transplantation of hepatocytes and hepatic stellate cells has been shown to increase the engraftment of transplanted hepatocytes in the liver. Here, we describe a method for the simultaneous isolation of human primary hepatocytes and hepatic stellate cells from the same donor for co-transplantation or for use in in vitro cell culture models.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830557/isolation-of-gmp-grade-human-hepatocytes-from-remnant-liver-tissue-of-living-donor-liver-transplantation
#10
Shin Enosawa
For the purpose of clinical research of hepatocyte transplantation, procedures for isolation, cryopreservation, thawing, and functional assessment of hepatocytes are described. Although demands for human hepatocytes are increasing in not only cell therapy but also drug development, it is highly difficult to obtain good lots of hepatocytes from human liver tissue. This chapter describes essential issues such as alleviation of warm ischemia, prevention of shear stress, optimization of cryopreservation, and functional assessment, along with securement of quality...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830556/deep-digging-far-red-imaging-for-the-monitoring-of-transplanted-hepatocytes-in-rats
#11
Peggy Stock, Kristin Weber
Technologies for in vivo imaging of the distribution and integration of cell transplants gain significance for the use of novel cell therapy approaches in regenerative medicine. Applied to adequate animal models, they provide information on the spatio-temporal engraftment and functional performance of the cells transplanted. This chapter includes a detailed description of the in vivo tracking of transplanted hepatocytes in rat liver including the conjugation of antibodies to fluorochromes for far red imaging using a multispectral optical imager...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830555/preclinical-swine-models-for-monitoring-of-hepatocyte-transplantation-by-mri
#12
Nathanael Raschzok, Ulf Teichgräber, Johann Pratschke, Igor M Sauer
Hepatocyte transplantation is a promising approach for treatment of certain liver disorders, especially for metabolic liver disease in the juvenile. The lack of a clinically approved noninvasive imaging technique is a major limitation to the further development of hepatocyte transplantation. Cell tracking by Magnetic Resonance Imaging (MRI) is a promising approach for noninvasive monitoring of the fate of transplanted cells. Studies in large animal models are necessary to transfer this promising technique into the clinic...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830554/minimally-invasive-liver-preconditioning-for-hepatocyte-transplantation-in-rats
#13
Martin Gaillard, Ibrahim Dagher
In the context of cell transplantation in the liver parenchyma, preconditioning is essential to enhance cell engraftment and liver repopulation. The authors have developed a minimally invasive technique of temporary portal embolization using an absorbable material, called reversible portal vein embolization. We hereby describe the method for isolating hepatocytes from a donor rat before transplanting hepatocytes after reversible portal vein embolization in the recipient.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830553/use-of-thymidine-kinase-recombinant-adenovirus-and-ganciclovir-mediated-mouse-liver-preconditioning-for-hepatocyte-xenotransplantation
#14
Daniel Moreno, Leire Neri, Eva Vicente, Africa Vales, Rafael Aldabe
Hepatocyte transplantation is the best approach to maintain and propagate differentiated hepatocytes from different species. Host liver has to be adapted for transplanted hepatocytes productive engraftment and proliferation being required a chronic liver injury to eliminate host hepatocytes and provide a proliferative advantage to the transplanted hepatocytes. Most valuable mouse models for xenograft hepatocyte transplantation are based on genetically modified animals to cause a chronic liver damage and to limit host hepatocyte regeneration potential...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830552/demonstrating-potential-of-cell-therapy-for-wilson-s-disease-with-the-long-evans-cinnamon-rat-model
#15
Fadi Luc Jaber, Yogeshwar Sharma, Sanjeev Gupta
Wilson's disease (WD) is characterized by the inability to excrete copper (Cu) from the body with progressive tissue injury, especially in liver and brain. The molecular defect in WD concerns mutations in ATP7B gene leading to loss of Cu transport from the hepatocyte to the bile canaliculus. While drugs, e.g., Cu chelators, have been available for several decades, these must be taken lifelong, which can be difficult due to issues of compliance or side effects. Many individuals may require liver transplantation, which can also be difficult due to donor organ shortages...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830551/experimental-hepatocyte-transplantation-in-pigs
#16
Eiji Kobayashi, Shin Enosawa, Hiroshi Nagashima
Technical issues of experimental hepatocyte transplantation in pigs, i.e., selection of animals, anesthesia, route of transplantation, and segment-specific transplantation have described.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830550/gunn-rats-as-a-surrogate-model-for-evaluation-of-hepatocyte-transplantation-based-therapies-of-crigler-najjar-syndrome-type-1
#17
Zsuzsanna Polgar, Yanfeng Li, Xia Li Wang, Chandan Guha, Namita Roy-Chowdhury, Jayanta Roy-Chowdhury
Liver transplantation has been established as a curative therapy for acute and chronic liver failure, as well as liver-based inherited metabolic diseases. Because of the complexity of organ transplantation and the worldwide shortage of donor organs, hepatocyte transplantation is being developed as a bridging therapy until donor organs become available, or for amelioration of inherited liver-based diseases. The Gunn rat is a molecular and metabolic model of Crigler-Najjar syndrome type 1, which is characterized by lifelong unconjugated hyperbilirubinemia due to the lack of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-mediated bilirubin glucuronidation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830547/propagation-of-human-hepatocytes-in-upa-scid-mice-producing-chimeric-mice-with-humanized-liver
#18
Hiroki Ohshita, Chise Tateno
Primary or cryopreserved human hepatocytes (h-heps) have been used as the gold standard for in vitro metabolism and hepatotoxicity studies; however, the supply of h-heps is limited and they cannot grow in vitro. We achieved approximately 1000-fold propagation of h-heps in the liver of albumin promoter/enhancer-driven urokinase-type plasminogen activator transgenic/severe combined immunodeficiency disease (uPA/SCID) mice with genetically induced liver disease and immunodeficiency. When h-heps are transplanted into the uPA/SCID mouse liver via the spleen, the h-heps engraft in the mouse liver, resulting in its repopulation with h-heps...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830545/a-modified-protocol-for-the-isolation-of-primary-human-hepatocytes-with-improved-viability-and-function-from-normal-and-diseased-human-liver
#19
David C Bartlett, Philip N Newsome
Successful hepatocyte isolation is critical for continued development of cellular transplantation. However, most tissue available for research is from diseased liver and the results of hepatocyte isolation from such tissue are inferior compared to normal tissue. Here we describe a modified method, combining the use of Liberase and N-acetylcysteine (NAC), for the isolation of primary human hepatocytes with high viability from normal and diseased liver.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27830544/late-gestation-fetal-hepatocytes-for-liver-repopulation-in-the-rat
#20
Jennifer A Sanders
Cellular transplantation represents an alternative to liver transplantation for the treatment of end-stage liver disease and liver-based inborn errors of metabolism. In order for cellular transplantation to be successful, an optimal source of cells for transplantation needs to be identified and the molecular mechanisms regulating their engraftment, proliferation, and functional differentiation elucidated. Here we describe a detailed protocol for the isolation, selection, and transplantation into an injured adult rat liver of a defined population of late gestation fetal rat hepatocytes...
2017: Methods in Molecular Biology
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