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Hepatocyte transplantation

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https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#1
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319445/nonclinical-pharmacology-toxicology-study-of-aav8-tbg-mldlr-and-aav8-tbg-hldlr-in-a-mouse-model-of-homozygous-familial-hypercholesterolemia
#2
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
The homozygous form of familial hypercholesterolemia (HoFH) is an excellent model for developing in vivo gene therapy in humans. The success of orthotropic liver transplantation in correcting the metabolic abnormalities in HoFH suggests that the correction of low-density lipoprotein receptor (LDLR) expression in hepatocytes via gene therapy should be sufficient for therapeutic efficacy. Vectors based on adeno-associated virus serotype 8 (AAV8) have been previously developed for liver-targeted gene therapy of a number of genetic diseases, including HoFH...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28297787/-umbilical-cord-mesenchymal-stem-cells-and-their-association-with-liver-fibrosis
#3
L Tuo, W Z Zeng, H L Xue, X L Wu
At present, the most effective therapeutic method for end-stage liver fibrosis is liver transplantation. However, the application of liver transplantation is limited by a shortage of liver donors, a high incidence rate of surgical complications, graft-versus-host disease, and high medical costs. Umbilical cord mesenchymal stem cell (UC-MSC) transplantation may become a promising method for the treatment of liver diseases. UC-MSCs are adult stem cells which exhibit multipotential differentiation and can differentiate into hepatic parenchymal cells...
January 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28297588/oncostatin-m-preconditioned-mesenchymal-stem-cells-alleviate-bleomycin-induced-pulmonary-fibrosis-through-paracrine-effects-of-the-hepatocyte-growth-factor
#4
Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong-Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong
Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28296681/adenovirus-hepatitis-clinicopathologic-analysis-of-12-consecutive-cases-from-a-single-institution
#5
Kurt B Schaberg, Neeraja Kambham, Richard K Sibley, John P T Higgins
Adenoviruses are common pathogens that usually cause self-limited infections. However, in the immunocompromised host they can cause severe infections involving multiple organs including the liver. A search of the pathology database at Stanford University Medical Center (1995 to 2016) identified 12 cases of adenovirus hepatitis including biopsy and autopsy specimens. There were 8 pediatric patients, 7 of which had received orthotropic liver transplants and 1 of which was receiving chemotherapy for lymphoblastic leukemia...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28284982/the-balance-between-cd8-t-cell-mediated-clearance-of-aav-encoded-antigen-in-the-liver-and-tolerance-is-dependent-on-the-vector-dose
#6
Sandeep R P Kumar, Brad E Hoffman, Cox Terhorst, Ype P de Jong, Roland W Herzog
The liver continuously receives antigens from circulation and the gastrointestinal tract. A complex immune regulatory system has evolved in order to both limit inflammation and promote tolerance in the liver. Although in situ immune tolerance mechanisms enable successful gene therapy and liver transplantation, at the same time they facilitate chronic infections by pathogens such as hepatitis viruses. It is, however, poorly understood why hepatocytes infected with hepatitis viruses or transduced with adeno-associated virus (AAV)-based vectors may be rejected by CD8(+) T cells several months later...
March 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28279229/human-umbilical-cord-mesenchymal-stem-cells-improve-the-reserve-function-of-perimenopausal-ovary-via-a-paracrine-mechanism
#7
Jia Li, QiuXian Mao, JingJun He, HaoQing She, Zhi Zhang, ChunYan Yin
BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. We designed this experimental study in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence. METHOD: We selected naturally aging rats confirmed by vaginal smears as models of perimenopausal rats, divided into the control group and the treatment group, and selected young fertile female rats as normal controls...
March 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28275217/identification-of-proteins-interacting-with-cytoplasmic-high-mobility-group-box-1-during-the-hepatocellular-response-to-ischemia-reperfusion-injury
#8
Tianjiao Zhang, Weiwei Wei, Olaf Dirsch, Thomas Krüger, Chunyi Kan, Chichi Xie, Olaf Kniemeyer, Haoshu Fang, Utz Settmacher, Uta Dahmen
Ischemia/reperfusion injury (IRI) occurs inevitably in liver transplantations and frequently during major resections, and can lead to liver dysfunction as well as systemic disorders. High-mobility group box 1 (HMGB1) plays a pathogenic role in hepatic IRI. In the normal liver, HMGB1 is located in the nucleus of hepatocytes; after ischemia reperfusion, it translocates to the cytoplasm and it is further released to the extracellular space. Unlike the well-explored functions of nuclear and extracellular HMGB1, the role of cytoplasmic HMGB1 in hepatic IRI remains elusive...
January 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28275009/paracrine-signals-regulate-human-liver-organoid-maturation-from-ipsc
#9
Akihiro Asai, Eitaro Aihara, Carey Watson, Reena Mourya, Tatsuki Mizuochi, Pranavkumar Shivakumar, Kieran Phelan, Christopher Mayhew, Michael Helmrath, Takanori Takebe, James Wells, Jorge A Bezerra
A self-organizing organoid model provides a new approach to study the mechanism of human liver organogenesis. Previous animal models documented that simultaneous paracrine signaling and cell-to-cell surface contact regulate hepatocyte differentiation. To dissect the relative contributions of the paracrine effects, we first established a liver organoid using human induced pluripotent stem cells (iPSC), mesenchymal stem cells (MSC), and human umbilical vein endothelial cells (HUVEC) as previously reported. Time-lapse imaging showed the iPSC-derived hepatic endoderm (HE-iPSC) self-assembled into three-dimensional organoids, resulting in hepatic gene induction...
March 8, 2017: Development
https://www.readbyqxmd.com/read/28273635/nobiletin-ameliorates-ischemia-reperfusion-injury-by-suppressing-the-function-of-kupffer-cells-after-liver-transplantation-in-rats
#10
Yakun Wu, Wenfeng Zhang, Min Li, Ding Cao, Xiaoli Yang, Jianping Gong
This study aims to explore the protective effects of nobiletin against hepatic ischemia-reperfusion (IR) injury after liver transplantation. Kupffer cells (KCs) were activated and co-cultured with different concentration of nobiletin for 24h in vitro, inflammatory products and activity of TLR4/NF-κB signaling pathway were detected. Sprague-Dawley rats were selected and underwent orthotopic liver transplantation. Donors were injected intravenously with nobiletin (50mg/kg) or saline solution, once a day for 1 week before the surgery...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28273362/tlr5-signaling-restrains-t-nkt-cell-activation-and-protects-against-concanavalin-a-induced-hepatic-injury
#11
Lei Wang, Wen Zhang, Chang-Hui Ge, Rong-Hua Yin, Xiao Yang, Yi-Qun Zhan, Miao Yu, Chang-Yan Li, Zhi-Qiang Ge, Xiao-Ming Yang
TLR5 signaling regulates the immune privileged status of the liver and is involved in hepatic immune disorders. However, the role of TLR5 has not yet been investigated in experimental models of Con A-mediated liver injury. Here, we show that TLR5 is highly upregulated in the hepatic mononuclear cells (MNCs) of mice during Con A-induced hepatitis. Increased mortality and liver histopathology of TLR5-deficient mice correlated with excessive production of pro-inflammatory cytokines, suggesting that TLR5 knockout mice were more susceptible to Con A-induced hepatitis...
March 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28271982/hepatic-mir-301a-as-a-liver-transplant-rejection-biomarker-and-its-role-for-interleukin-6-production-in-hepatocytes
#12
Toshiaki Nakano, I-Hsuan Chen, Shigeru Goto, Chia-Yun Lai, Hui-Peng Tseng, Li-Wen Hsu, King-Wah Chiu, Chih-Che Lin, Chih-Chi Wang, Yu-Fan Cheng, Chao-Long Chen
Acute rejection (AR) of liver transplantation remains a formidable challenge for diagnostic medicine and biomarker discovery. We characterized AR-related microRNAs (miRNAs) and the underlying AR mechanisms in liver transplantation. Using a rat model of orthotopic liver transplantation (OLT) as well as microarrays, we compared the miRNA expression profiles between naive and AR livers on day 7 after OLT with short- (<14 days, donor Dark Agouti [DA] liver into Lewis [LEW] recipient) and long-term (>60 days, donor DA liver into Piebald Virol Glaxo [PVG] recipient) survival fates...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28266658/targeted-antigen-delivery-to-dendritic-cells-elicits-robust-antiviral-t-cell-mediated-immunity-in-the-liver
#13
Julia Volckmar, Marcus Gereke, Thomas Ebensen, Peggy Riese, Lars Philipsen, Stefan Lienenklaus, Dirk Wohlleber, Robert Klopfleisch, Sabine Stegemann-Koniszewski, Andreas J Müller, Achim D Gruber, Percy Knolle, Carlos A Guzman, Dunja Bruder
Hepatotropic viruses such as hepatitis C virus cause life-threatening chronic liver infections in millions of people worldwide. Targeted in vivo antigen-delivery to cross-presenting dendritic cells (DCs) has proven to be extraordinarily efficient in stimulating antigen-specific T cell responses. To determine whether this approach would as well be suitable to induce local antiviral effector T cells in the liver we compared different vaccine formulations based on either the targeting of DEC-205 or TLR2/6 on cross-presenting DCs or formulations not involving in vivo DC targeting...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261903/testing-of-microencapsulated-porcine-hepatocytes-in-a-new-model-of-fulminant-liver-failure-in-baboons
#14
Zurab Machaidze, Heidi Yeh, Lingling Wei, Christian Schuetz, Michele Carvello, Antonino Sgroi, Rex N Smith, Henk-Jan Schuurman, David H Sachs, Philippe Morel, James F Markmann, Léo H Bühler
BACKGROUND: There is no standard therapy for acute liver failure. Hepatocyte transplantation has been proposed for temporary liver function support, while the injured liver regenerates or while waiting for transplantation. We have previously shown such efficacy for microencapsulated porcine hepatocytes in mice with fulminant liver failure. We aimed to establish a large animal model for fulminant liver failure to assess the efficacy of microencapsulated porcine hepatocytes in temporary liver function support...
March 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28253324/interferon-alpha-treatment-stimulates-interferon-gamma-expression-in-type-i-nkt-cells-and-enhances-their-antiviral-effect-against-hepatitis-c-virus
#15
Eisuke Miyaki, Nobuhiko Hiraga, Michio Imamura, Takuro Uchida, Hiromi Kan, Masataka Tsuge, Hiromi Abe-Chayama, C Nelson Hayes, Grace Naswa Makokha, Masahiro Serikawa, Hiroshi Aikata, Hidenori Ochi, Yuji Ishida, Chise Tateno, Hideki Ohdan, Kazuaki Chayama
Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28252220/metabolic-oscillations-in-co-cultures-of-hepatocytes-and-mesenchymal-stem-cells-effects-of-seeding-arrangement-and-culture-mixing
#16
Dalia Abdelrahim Alzebdeh, Howard William Matthew
In vitro assembly of functional liver tissue is a prerequisite for the transplantation of tissue-engineered livers. There is an increasing demand for in vitro models that replicate complex events occurring in the liver. However, tissue engineering of implantable liver systems is currently limited by the difficulty of assembling three dimensional hepatocyte cultures of a useful size, while maintaining full cell viability. Recent reports have demonstrated that bone marrow mesenchymal stem cells (BM-MSCs) can provide a number of cues promoting hepatocyte growth and development...
March 2, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28247264/new-paradigms-in-management-of-alcoholic-hepatitis-a-review
#17
REVIEW
Sandeep Singh Sidhu, Omesh Goyal, Harsh Kishore, Simran Sidhu
Severe alcoholic hepatitis (SAH) is defined by modified Maddrey discriminant function ≥32 or Model for End-Stage Liver Disease (MELD) >21 and/or hepatic encephalopathy. It has a 3-month mortality rate ≥30-70 %. Patients with severe alcoholic hepatitis need combined, i.e., static (MELD score) and dynamic (Lille's score), prognostication. Systemic inflammation and poor regeneration are hallmarks of SAH, rather than intrahepatic inflammation. SAH is characterized by dysregulated and uncontrolled systemic inflammatory response followed by weak compensatory antiinflammatory response that leads to increased susceptibility to infection and multiple organ failure...
February 28, 2017: Hepatology International
https://www.readbyqxmd.com/read/28223721/current-and-future-therapies-for-inherited-cholestatic-liver-diseases
#18
REVIEW
Wendy L van der Woerd, Roderick Hj Houwen, Stan Fj van de Graaf
Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phenotypes range from benign recurrent intrahepatic cholestasis (BRIC), associated with recurrent cholestatic attacks, to progressive FIC (PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency (PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency (PFIC1 and PFIC2)...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28220319/cfd-assessment-of-the-effect-of-convective-mass-transport-on-the-intracellular-clearance-of-intracellular-triglycerides-in-macrosteatotic-hepatocytes
#19
Gabriel Yarmush, Lucas Santos, Joshua Yarmush, Srivathsan Koundinyan, Mubasher Saleem, Nir I Nativ, Martin L Yarmush, Francois Berthiaume, Timothy J Maguire, Chris Guaghan
Donor livers available to transplant for patients with end-stage liver disease are in severe shortage. One possible avenue to expand the donor pool is to recondition livers that would be otherwise discarded due to excessive fat content. Severely steatotic livers (also known as fatty livers) are highly susceptible to ischemia-reperfusion injury and as a result, primary liver non-function post-transplantation. Prior studies in isolated perfused rat livers suggest that "defatting" may be possible in a timeframe of a few hours; thus, it is conceivable that fatty liver grafts could be recovered by machine perfusion to clear stored fat from the organ prior to transplantation...
February 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28217369/regenerative-medicine-using-dental-pulp-stem-cells-for-liver-diseases
#20
EDITORIAL
Shogo Ohkoshi, Hajime Hara, Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa
Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
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