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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/28648365/direct-reprogramming-of-fibroblasts-via-a-chemically-induced-xen-like-state
#1
Xiang Li, Defang Liu, Yantao Ma, Xiaomin Du, Junzhan Jing, Lipeng Wang, Bingqing Xie, Da Sun, Shaoqiang Sun, Xueqin Jin, Xu Zhang, Ting Zhao, Jingyang Guan, Zexuan Yi, Weifeng Lai, Ping Zheng, Zhuo Huang, Yanzhong Chang, Zhen Chai, Jun Xu, Hongkui Deng
Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)-like state. Here, we show that these chemically induced XEN-like cells can also be induced to directly reprogram into functional neurons, bypassing the pluripotent state. The induced neurons possess neuron-specific expression profiles, form functional synapses in culture, and further mature after transplantation into the adult mouse brain...
June 20, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28646508/hepatic-stimulator-substance-resists-hepatic-ischemia-reperfusion-injury-by-regulating-drp1-translocation-and-activation
#2
Chao Zhang, Jing Huang, Wei An
Ischemia-reperfusion injury (IRI), induced by abnormal mitochondrial fission related apoptosis, is a major concern in liver transplantation settings. Our previous studies have demonstrated that hepatic stimulator substance (HSS) is an anti-apoptotic effector and could protect liver from IRI. However, the underlying mechanism remains unclear. In the present study, we report that in vitro and in vivo HSS could regulate mitochondrial fission and hepatocyte apoptosis during liver IRI by orchestrating the translocation and activation of dynamin-related protein 1 (Drp1)...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646094/immune-mediated-effects-targeting-hepatitis-c-virus-in-a-syngeneic-replicon-cell-transplantation-mouse-model
#3
Sepideh Levander, Fredrik Holmström, Lars Frelin, Gustaf Ahlén, Daniel Rupp, Gang Long, Ralf Bartenschlager, Matti Sällberg
OBJECTIVE: HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells. DESIGN: A total of 5 million H-2(b) positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2(b)-restricted mice...
June 23, 2017: Gut
https://www.readbyqxmd.com/read/28640790/microrna-155-deficiency-in-kupffer-cells-ameliorates-liver-ischemia-reperfusion-injury-in-mice
#4
Yakun Li, Dongxia Ma, Zhimin Wang, Jun Yang
BACKGROUND: MicroRNA-155 (miR-155) is known to be involved in autoimmune diseases, inflammation, and transplantation. However, its role in a warm hepatic ischemia-reperfusion (IR) model has not been fully elucidated. METHODS: Partial hepatic IR was performed in wild-type and miR-155-deficient mice treated with or without GdCl3, and then the serum transaminase concentration and histology were analyzed. Kupffer cells (KCs) were isolated from the liver after IR, and immunohistochemistry was used to evaluate activation and polarization...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28640507/a-liver-specific-gene-expression-panel-predicts-the-differentiation-status-of-in-vitro-hepatocyte-models
#5
Dae-Soo Kim, Jea-Woon Ryu, Mi-Young Son, Jung-Hwa Oh, Kyung-Sook Chung, Sugi Lee, Jeong-Ju Lee, Jun-Ho Ahn, Ju-Sik Min, Jiwon Ahn, Hyun Mi Kang, Janghwan Kim, Cho-Rok Jung, Nam-Soon Kim, Hyun-Soo Cho
Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional (3D) organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies...
June 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28630420/functional-evaluation-of-a-bioartificial-liver-support-system-using-immobilized-hepatocyte-spheroids-in-a-porcine-model-of-acute-liver-failure
#6
Ji-Hyun Lee, Doo-Hoon Lee, Sanghoon Lee, Choon Hyuck David Kwon, Jae-Nam Ryu, Jeong-Kwon Noh, In Keun Jang, Hey-Jung Park, Hee-Hoon Yoon, Jung-Keug Park, Young-Jin Kim, Sung-Koo Kim, Suk-Koo Lee
Bioartificial livers (BAL) may offer acute liver failure (ALF) patients an opportunity for cure without liver transplantation. We evaluated the efficacy of a spheroid-based BAL system, containing aggregates of porcine hepatocytes, in a porcine model of ALF. ALF pigs were divided into three groups. The control group consisted of treatment naïve pigs (n = 5), blank group consisted of pigs that were attached to the BAL system not containing hepatocytes for 12 hours (n = 5) and BAL group consisted of pigs that were attached to the BAL containing hepatocytes for 12 hours (n = 5)...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625011/liver-epithelioid-progenitor-cells-derived-from-fetal-luxi-bovine-alleviate-liver-fibrosis
#7
Kunfu Wang, Hao Liu, Jinjuan Yang, Caiyun Ma, Zebiao Zhang, Dong Zheng, Weijun Guan
Liver epithelioid progenitor cells (LEPCs) have important roles in liver therapy because of their hepatic differentiation potency in vitro and in vivo. Despite many researches on humans, mice, and rats, equivalent progenitor cells derived from bovine are relatively rare. The purpose of our current study is to characterize bovine LEPCs, and research on the cure potency of this heteroplastic progenitor cells on mice liver fibrosis. We have used collagenase IV digesting and differential adhesion method to isolate slabstone shape, EpCAM, LGR5, NCAM1 and SOX9 positive progenitor cells from fetal Luxi bovine liver...
June 17, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28624103/from-organoids-to-organs-bioengineering-liver-grafts-from%C3%A2-hepatic-stem-cells-and-matrix
#8
REVIEW
Jorke Willemse, Ruby Lieshout, Luc J W van der Laan, Monique M A Verstegen
Due to the complex function and structure of the liver, resourceful solutions for treating end-stage liver disease are required. Currently, liver transplantation is the only curative therapeutic option. However, due to a worldwide donor shortage, researchers have been looking in other fields for alternative sources of transplantable liver tissue. Recent advances in our understanding of liver physiology, stem cell and matrix biology, have accelerated tissue engineering research. Most notable is the discovery of a culture system to grow liver-like organoids from human hepatic stem cells...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28620221/mesenchymal-stem-cell-derived-exosomes-as-a-new-therapeutic-strategy-for-liver-diseases
#9
REVIEW
Guohua Lou, Zhi Chen, Min Zheng, Yanning Liu
The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. However, the risks of iatrogenic tumor formation, cellular rejection and infusional toxicity in MSC transplantation remain unresolved. Accumulating evidence now suggests that a novel cell-free therapy, MSC-secreted exosomes, might constitute a compelling alternative because of their advantages over the corresponding MSCs...
June 16, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28619106/bone-mesenchymal-stem-cells-ameliorate-ischemia-reperfusion-induced-damage-in-renal-epithelial-cells-via-microrna-223
#10
Xiaopeng Yuan, Xiaoping Wang, Chuanbao Chen, Jian Zhou, Ming Han
BACKGROUND: Recent studies have indicated that microRNA-223 (miR-223) plays a role in the tissue-protective effect of mesenchymal stem cells (MSCs). NLR family-pyrin domain containing 3 (NLRP3) was reported to affect a renal ischemia/reperfusion (I/R) injury by exerting a direct effect on the renal tubular epithelium. Therefore, we investigated how miR-223 and NLRP3 might function in kidneys exposed to conditions of ischemia and subsequent reperfusion. METHODS: Hypoxia/reoxygenation (H/R) murine renal tubular epithelial cells (RTECs) were cocultured with either MSCs or hypoxia-pretreated MSCs (htMSCs), after which the RTECs were examined for their viability and evidence of apoptosis...
June 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28602611/dna-methyltransferases-modulate-hepatogenic-lineage-plasticity-of%C3%A2-mesenchymal-stromal-cells
#11
Chien-Wei Lee, Wei-Chih Huang, Hsien-Da Huang, Yi-Hsiang Huang, Jennifer H Ho, Muh-Hwa Yang, Vincent W Yang, Oscar K Lee
The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor β1 (TGFβ1), which in turn controls hepatogenic differentiation and de-differentiation...
June 1, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28596681/effects-of-heme-oxygenase-1-modified-bone-marrow-mesenchymal-stem-cells-on-microcirculation-and-energy-metabolism-following-liver-transplantation
#12
Liu Yang, Zhong-Yang Shen, Rao-Rao Wang, Ming-Li Yin, Wei-Ping Zheng, Bin Wu, Tao Liu, Hong-Li Song
AIM: To investigate the effects of heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation (RLT) in a rat model. METHODS: BMMSCs were isolated and cultured in vitro using an adherent method, and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs. A rat acute rejection model following 50% RLT was established using a two-cuff technique...
May 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28594937/hyperferritinemia-and-hypergammaglobulinemia-predict-the-treatment-response-to-standard-therapy-in-autoimmune-hepatitis
#13
Richard Taubert, Matthias Hardtke-Wolenski, Fatih Noyan, Claudine Lalanne, Danny Jonigk, Jerome Schlue, Till Krech, Ralf Lichtinghagen, Christine S Falk, Verena Schlaphoff, Heike Bantel, Luigi Muratori, Michael P Manns, Elmar Jaeckel
Autoimmune hepatitis (AIH) is a chronic hepatitis with an increasing incidence. The majority of patients require life-long immunosuppression and incomplete treatment response is associated with a disease progression. An abnormal iron homeostasis or hyperferritinemia is associated with worse outcome in other chronic liver diseases and after liver transplantation. We assessed the capacity of baseline parameters including the iron status to predict the treatment response upon standard therapy in 109 patients with untreated AIH type 1 (AIH-1) in a retrospective single center study...
2017: PloS One
https://www.readbyqxmd.com/read/28589248/quercetin-and-tin-protoporphyrin-attenuate-hepatic-ischemia-reperfusion-injury-role-of-ho-1
#14
Yara Atef, Hassan M El-Fayoumi, Yousra Abdel-Mottaleb, Mona F Mahmoud
Ischemia reperfusion (IR) injury occurs in many clinical situations such as organ transplantation and hepatectomies resulting in oxidative stress and immune activation. Heme oxygenase-1(HO-1) is the rate-limiting step in the heme-degradation pathway and has a critical cytoprotective role. Induction of HO-1 improves liver I/R injury. Quercetin, a plant pigment (flavonoid), is an antioxidant and HO-1 inducer. Tin protoporphyrin (SnPP) is a HO-1 inhibitor. This study was designed to investigate the protective effect of quercetin in hepatic I/R injury and the role of HO-1...
June 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28586545/multifaceted-therapeutic-benefits-of-factors-derived-from-stem-cells-from-human-exfoliated-deciduous-teeth-for-acute-liver-failure-in-rats
#15
Yoshihiro Matsushita, Masatoshi Ishigami, Kohki Matsubara, Megumi Kondo, Hirotaka Wakayama, Hidemi Goto, Minoru Ueda, Akihito Yamamoto
In acute liver failure (ALF), a poorly controlled innate immune response causes massive hepatic destruction, which elicits a systemic inflammatory response, progressive multiple organ failure and ultimate sudden death. Although the liver has inherent tissue-repairing activities, its regeneration during ALF fails, and orthotopic liver transplantation is the only curative approach. Here we show that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) into the d-galactosamine-induced rat model of ALF markedly improved the condition of the injured liver and the animals' survival rate...
June 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28585911/transplant-of-hepatocytes-undifferentiated-mesenchymal-stem-cells-and-in-vitro-hepatocyte-differentiated-mesenchymal-stem-cells-in-a-chronic-liver-failure-experimental-model-a-comparative-study
#16
Hanan El Baz, Zeinab Demerdash, Manal Kamel, Shimaa Atta, Faten Salah, Salwa Hassan, Olfat Hammam, Heba Khalil, Safa Meshaal, Inas Raafat
OBJECTIVES: Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure...
June 5, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28574625/patatin-like-phospholipase-domain-containing-3-gene-as-a-liver-steatosis-risk-factor-following-living-donor-liver-transplantation-for-hepatitis-c
#17
Hisamitsu Miyaaki, Satoshi Miuma, Naota Taura, Hidetaka Shibata, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Susumu Eguchi, Kazuhiko Nakao
Liver steatosis frequently occurs following liver transplantation (LT) and can affect patient outcome. Here, we aimed to clarify the steatosis and steatohepatitis risk factors that apply after living-donor LT for chronic hepatitis C.We retrospectively examined 43 transplant recipients and donors, and tested for single-nucleotide polymorphisms in the patatin-like phospholipase domain-containing 3 gene (PNPLA3). Liver biopsies taken 1 year after transplantation and yearly thereafter, or when abnormal liver enzyme levels were detected, were examined by histopathology...
June 2, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28574111/isolation-characterization-and-cold-storage-of-cells-isolated-from-diseased-explanted-livers
#18
Elisa Belaschk, Susanne Rohn, Ramla Mukiibi, Anja Reutzel-Selke, Peter Tang, Birgit Sawitzki, Johann Pratschke, Igor M Sauer, Martina T Mogl
INTRODUCTION: Livers discarded after standard organ retrieval are commonly used as a cell source for hepatocyte transplantation. Due to the scarcity of organ donors, this leads to a shortage of suitable cells for transplantation. Here, the isolation of liver cells from diseased livers removed during liver transplantation is studied and compared to the isolation of cells from liver specimens obtained during partial liver resection. METHODS: Hepatocytes from 20 diseased explanted livers (Ex-group) were isolated, cultured and stored at 4°C for up to 48 hours, and compared to hepatocytes isolated from the normal liver tissue of 14 liver lobe resections (Rx-group)...
May 23, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28573188/a-hyper-crosslinked-carbohydrate-polymer-scaffold-facilitates-lineage-commitment-and-maintains-a-reserve-pool-of-proliferating-cardiovascular-progenitors
#19
Jonathan M Baio, Ryan C Walden, Tania I Fuentes, Charles C Lee, Nahidh W Hasaniya, Leonard L Bailey, Mary K Kearns-Jonker
BACKGROUND: Cardiovascular progenitor cells (CPCs) have been cultured on various scaffolds to resolve the challenge of cell retention after transplantation and to improve functional outcome after cell-based cardiac therapy. Previous studies have reported successful culture of fully differentiated cardiomyocytes on scaffolds of various types, and ongoing efforts are focused on optimizing the mix of cardiomyocytes and endothelial cells as well as on the identification of a source of progenitors capable of reversing cardiovascular damage...
May 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28564720/inflammasomes-in-liver-fibrosis
#20
Fernando Alegre, Pablo Pelegrin, Ariel E Feldstein
Cell death and inflammation are two central elements in the development of liver fibrosis. Inflammasomes are intracellular multiprotein complexes expressed in both hepatocytes and nonparenchymal cells in the liver that are key regulators of inflammation and cell fate. They respond to cellular danger signals by activating caspase 1, releasing the proinflammatory cytokines IL-1β and IL-18, as well as initiating a novel pathway of programmed cell death termed "pyroptosis." These processes can initiate and perpetuate an abnormal wound-healing response with the principle cellular target being the activation of hepatic stellate cells...
May 2017: Seminars in Liver Disease
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