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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/29775791/an-imaging-biomarker-for-assessing-hepatic-function-in-patients-with-primary-sclerosing-cholangitis
#1
Jennifer Schulze, Henrike Lenzen, Jan B Hinrichs, Burckhardt Ringe, Michael P Manns, Frank Wacker, Kristina I Ringe
BACKGROUND & AIMS: We aimed to evaluate the potential of hepatobiliary phase magnetic resonance imaging (MRI) as parameter for assessment of hepatocellular function in patients with primary sclerosing cholangitis (PSC). METHODS: We collected data from 111 patients (83 male, 28 female; median, 44 years old), from March 2012 through March 2016, with a confirmed diagnosis of PSC who underwent MRI evaluation before and after injection (hepatobiliary phase) of a hepatocyte-specific contrast agent (gadoxetate disodium)...
May 15, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29774638/loss-of-sirtuin-1-and-mitofusin-2-contributes-to-enhanced-ischemia-reperfusion-injury-in-aged-livers
#2
Sung Kook Chun, Sooyeon Lee, Joseph Flores-Toro, Rebecca Y U, Ming-Jim Yang, Kristina L Go, Thomas G Biel, Catherine E Miney, Schiley Pierre Louis, Brian K Law, Mary E Law, Elizabeth M Thomas, Kevin E Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim
Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29764210/curative-ex-vivo-hepatocyte-directed-gene-editing-in-a-mouse-model-of-hereditary-tyrosinemia-type-1
#3
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/29761416/bioluminescence-imaging-of-transplanted-mesenchymal-stem-cells-by-overexpression-of-hepatocyte-nuclear-factor4%C3%AE-tracking-biodistribution-and-survival
#4
Peiyi Xie, Xiaojun Hu, Dan Li, Sidong Xie, Zhiyang Zhou, Xiaochun Meng, Hong Shan
PURPOSE: The purposes of this study were to construct immortalized human bone marrow mesenchymal stem cells (UE7T-13) with overexpression of the hepatocyte nuclear factor4α (hHNF4α) and luciferase2-mKate2 dual-fusion reporter gene, further investigate their impact on treating acute liver injury (ALI) in rats, and track their biodistribution and survival by bioluminescence imaging (BLI). PROCEDURES: The hHNF4α and luciferase2-mKate2 genes were transduced by a lentiviral vector into UE7T-13 cells (named E7-hHNF4α-R cells), and expression was verified by immunofluorescence, RT-PCR, and flow cytometry...
May 14, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29760366/-contribution-of-chimeric-mice-with-a-humanized-liver-to-the-evaluation-of-pharmacology-toxicity-and-pharmacokinetics-in-drug-discovery-and-development
#5
Seigo Sanoh, Shigeru Ohta
To develop new drugs with high efficacy and safety, it is important to predict the pharmacological, toxicological, and pharmacokinetic profiles of drug candidates in humans. Chimeric mice with a humanized liver are mice in which human hepatocytes have been transplanted, such that mouse liver cells are replaced with human hepatocytes; these mice have been used as prediction models. Studies performed thus far indicate that chimeric mice with a humanized liver can be used for the prediction of human-specific metabolite formation and plasma concentration-time curves for several drugs...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29745615/-progress-in-hepatocyte-status-detection-and-its-application-in-bioartificial-liver-support-system
#6
REVIEW
Shichen Xu, Changzhe Wu, Guanghao Zhang, Cheng Zhang, Xiaolin Huo
Bioartificial liver support system (BALSS) provides a new way to treat liver failure and leaves more time for patients who are waiting for liver transplantation. It has detoxification function as well as the human liver, at the same time it can provide nutrition and improve the internal environment inside human body. Bioreactors and hepatocytes with good biological activity are the cores of BALSS which determine the treatment effect. However, in the course of prolonged treatment, the function and activity of hepatocytes might be greatly changed which could influence the efficacy...
February 1, 2018: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
https://www.readbyqxmd.com/read/29742804/monocyte-chemoattractant-protein-induced-protein-1-targets-hypoxia-inducible-factor-1%C3%AE-to-protect-against-hepatic-ischemia-reperfusion-injury
#7
Peng Sun, Yue-Xin Lu, Daqing Cheng, Kuo Zhang, Jilin Zheng, Yupeng Liu, Xiaozhan Wang, Yu-Feng Yuan, Yi-Da Tang
Sterile inflammation is an essential factor causing hepatic ischemia/reperfusion (I/R) injury. As a critical regulator of inflammation, the role of monocyte chemoattractant protein-induced protein 1 (MCPIP1) in hepatic I/R injury remains undetermined. In this study, we discovered that MCPIP1 downregulation was associated with hepatic I/R injury in liver transplant patients and a mouse model. Hepatocyte-specific Mcpip1 gene knockout (HKO) and transgenic (HTG) mice demonstrated that MCPIP1 functions to ameliorate liver damage, reduce inflammation, prevent cell death, and promote regeneration...
May 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29735581/small-animal-models-of-hepatitis-e-virus-infection
#8
Tian-Cheng Li, Takaji Wakita
Novel hepeviruses have been recovered from many different animal species in recent years, increasing the diversity known to exist among the Hepeviridae , which now include two genera, Piscihepevirus and Orthohepevirus Multiple viral genotypes in the Orthohepevirus A species are able to replicate and cause acute hepatitis E in humans, and thus represent an important public health problem in industrialized as well as developing countries. Although hepatitis E virus (HEV) infections typically result in acute and self-limited hepatitis, immunocompromised and transplant patients are vulnerable to prolonged infections and to chronic hepatitis...
May 7, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29732274/clinical-hepatocyte-transplantation-what-is-next
#9
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/29731771/undifferentiated-adipose-tissue-stem-cell-transplantation-promotes-hepatic-regeneration-ameliorates-histopathologic-damage-of-the-liver-and-upregulates-the-expression-of-liver-regeneration-and-liver-specific-genes-in-a-rat-model-of-partial-hepatectomy
#10
Konstantinos G Apostolou, Ioannis G Papanikolaou, Charalampos Katselis, Themistoklis Feretis, Dimitrios Kletsas, Manousos M Konstadoulakis, Maria Lymperi, Angelica A Saetta, Spiros Tsikalakis, George Agrogiannis, Efstratios Patsouris, George C Zografos, Apostolos E Papalois
Objective: Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). Methods: Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29724658/human-hepatocyte-transplantation-corrects-the-inherited-metabolic-liver-disorder-arginase-deficiency-in-mice
#11
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/29723851/transplantation-of-telocytes-attenuates-unilateral-ureter-obstruction-induced-renal-fibrosis-in-rats
#12
Long Zheng, Long Li, Guisheng Qi, Mushuang Hu, Chao Hu, Shuo Wang, Jiawei Li, Mingnan Zhang, Weitao Zhang, Yigang Zeng, Yi Zhang, Liping Li, Xuanchuan Wang, Miao Lin, Tongyu Zhu, Ruiming Rong
BACKGROUND/AIMS: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. METHODS: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29720662/de-novo-formation-of-the-biliary-system-by-tgf%C3%AE-mediated-hepatocyte-transdifferentiation
#13
Johanna R Schaub, Kari A Huppert, Simone N T Kurial, Bernadette Y Hsu, Ashley E Cast, Bryan Donnelly, Rebekah A Karns, Feng Chen, Milad Rezvani, Hubert Y Luu, Aras N Mattis, Anne-Laure Rougemont, Philip Rosenthal, Stacey S Huppert, Holger Willenbring
Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche 1 . Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development-the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS) 2 ...
May 2, 2018: Nature
https://www.readbyqxmd.com/read/29719629/improvement-of-non-alcoholic-steatohepatitis-by-hepatocyte-like-cells-generated-from-ipscs-with-oct4-sox2-klf4-parp1
#14
Yueh Chien, Chi-Shuan Huang, Hsin-Chi Lin, Kai-Hsi Lu, Ping-Hsing Tsai, Ying-Hsiu Lai, Kuan-Hsuan Chen, Shou-Dong Lee, Yi-Hsiang Huang, Chien-Ying Wang
The prevalence of nonalcoholic fatty liver disease (NAFLD) is usually increased with age. Non-alcoholic steatohepatitis (NASH), a serious form of NAFLD, may lead to cirrhosis and end-stage liver diseases. Induced pluripotent stem cells (iPSCs) hold promising potential in personalized medicine. Although obviation of c-Myc reduces tumorigenic risk, it also largely reduced the generation of iPSCs. Recently, Poly(ADP-ribose) polymerase 1 (Parp1) has been reported to enhance cell reprogramming. In this study, we demonstrated that forced expression of Oct4/Sox2/Klf4/Parp1 (OSKP) effectively promoted iPSC generation from senescent somatic cells from 18-month-old mouse...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719266/autologous-and-heterologous-cell-therapy-for-hemophilia-b-toward-functional-restoration-of-factor-ix
#15
Suvasini Ramaswamy, Nina Tonnu, Tushar Menon, Benjamin M Lewis, Kevin T Green, Derek Wampler, Paul E Monahan, Inder M Verma
Hemophilia B is an ideal target for gene- and cell-based therapies because of its monogenic nature and broad therapeutic index. Here, we demonstrate the use of cell therapy as a potential long-term cure for hemophilia B in our FIX-deficient mouse model. We show that transplanted, cryopreserved, cadaveric human hepatocytes remain functional for more than a year and secrete FIX at therapeutic levels. Hepatocytes from different sources (companies and donors) perform comparably in curing the bleeding defect. We also generated induced pluripotent stem cells (iPSCs) from two hemophilia B patients and corrected the disease-causing mutations in them by two different approaches (mutation specific and universal)...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29719210/cell-encapsulation-overcoming-barriers-in-cell-transplantation-in-diabetes-and-beyond
#16
Marco Farina, Jenolyn F Alexander, Usha Thekkedath, Mauro Ferrari, Alessandro Grattoni
Cell-based therapy is emerging as a promising strategy for treating a wide range of human diseases, such as diabetes, blood disorders, acute liver failure, spinal cord injury, and several types of cancer. Pancreatic islets, blood cells, hepatocytes, and stem cells are among the many cell types currently used for this strategy. The encapsulation of these "therapeutic" cells is under intense investigation to not only prevent immune rejection but also provide a controlled and supportive environment so they can function effectively...
April 29, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29710411/photobiomodulation-with-red-light-emitting-diodes-accelerates-hepatocytes-proliferation-through-reactive-oxygen-species-extracellular-signal-regulated-kinase-pathway
#17
Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Syuichi Iwahashi, Yu Saito, Mitsuo Shimada
AIM: Cell-based transplantation is an alternate method of liver transplantation to delay the on-set of end-stage liver diseases. For successful treatment, cells need to be expended in vitro expeditiously. However, autogenetic hepatocytes as the ideal cell source for therapy remain quiescence so proliferation is rare. While photobiomodulation therapy (PBT) has been used to stimulate some kinds of cell proliferation, it is unknown if red light emitting diodes (LED) irradiation can promote primary hepatocyte proliferation...
April 30, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29705277/endotoxin-metabolism-reflects-hepatic-functional-reserve-in-end-stage-liver-disease
#18
N Okada, Y Sanada, T Urahashi, Y Ihara, N Yamada, Y Hirata, T Katano, S Otomo, K Ushijima, K Mizuta
BACKGROUND: The hepatic clearance of endotoxin (Et) may reflect hepatic functional reserve and ischemic injury to hepatocytes. Therefore, we examined the relationships between Et activity (EA) and the metrics Pediatric End-Stage Liver Disease (PELD)/Model of End-Stage Liver Disease (MELD) score and alanine transaminase (ALT) levels in the postoperative period. METHODS: We performed 8 living-donor liver transplantations (LDLTs) for biliary atresia at our center from April 2012 to December 2012...
April 25, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29695258/cells-responsible-for-liver-mass-regeneration-in-rats-with-2-acetylaminofluorene-partial-hepatectomy-injury
#19
Chin-Sung Chien, Ya-Hui Chen, Hui-Ling Chen, Chiu-Ping Wang, Shang-Hsin Wu, Shu-Li Ho, Wen-Cheng Huang, Chun-Hsien Yu, Mei-Hwei Chang
BACKGROUND: Whether hepatic progenitor cells (HPCs)/oval cells regenerate liver mass upon chronic liver injury is controversial in mice and has not been conclusively proven in humans and rats. In this study, we examined which cell type-hepatocytes or oval cells-mediates liver regeneration in the classic rat 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) injury where AAF reversibly blocks hepatocyte proliferation, thereby inducing oval cell expansion after the regenerative stimulus of PH...
April 25, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29691598/hepatocyte-transplantation-and-advancements-in-alternative-cell-sources-for-liver-based-regenerative-medicine
#20
REVIEW
Charlotte A Lee, Siddharth Sinha, Emer Fitzpatrick, Anil Dhawan
Human hepatocyte transplantation has been actively perused as an alternative to liver replacement for acute liver failure and liver-based metabolic defects. Current challenges in this field include a limited cell source, reduced cell viability following cryopreservation and poor engraftment of cells into the recipient liver with consequent limited life span. As a result, alternative stem cell sources such as pluripotent stem cells, fibroblasts, hepatic progenitor cells, amniotic epithelial cells and mesenchymal stem/stromal cells (MSCs) can be used to generate induced hepatocyte like cells (HLC) with each technique exhibiting advantages and disadvantages...
April 24, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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