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1
Wu, Yue. "Generating Beta-cells from liver cells". Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420423.
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Tirnitz-Parker, Janina Elke Eleonore. "Primary culture and immortal cell lines as in vitro models to evaluate the role of TWEAK signalling in hepatic oval cells /". Connect to this title, 2007. http://theses.library.uwa.edu.au/adt-WU2008.0039.
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Harrison, Sean. "Liver cell types derived from pluripotent stem cells". Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/liver-cell-types-derived-from-pluripotent-stem-cells(7f39c3ec-facd-4c06-ab9a-7c171313eb05).html.
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Liver development involves the differentiation and interaction of both endoderm and mesoderm cell types. The role of the liver in drug metabolism makes it an important area of medical research. Mimicking embryonic liver development in vitro using human ESCs is a strategy used to differentiate liver cell types. These can then be used as a model playing a role in the development of drugs and the study of their hepatotoxicity and would also have potential for use in cell therapy and regenerative medicine. Differentiated hepatocyte-like cells were found to have more in common with liver cells than those of other organs, including the secretion of albumin and activity of proteins important in drug metabolism, CYP3A and CYP2D6. However the hepatocyte-like cells were found to more closely resemble fetal rather than adult hepatocytesOrganoid differentiation resulted in cells types which in vivo are both endoderm and mesoderm derived cells of the liver. Culture in this 3D system allowed the spontaneous acquisition of polarity by these cells and their formation into structures reminiscent of liver architecture. After treatment with the toxin 4,4′-diaminodiphenylmethane a cell type and structure specific dose response was observed which matches that described in vivo.
4
Lam, Shuk-pik. "Differentiation of mesenchymal stem cells (MSCs) into hepatocytes in acute liver injury". Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43085647.
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Warren, Alessandra. "Hepatic sinusoidal cells in liver immunology and ageing". Thesis, The University of Sydney, 2005. https://hdl.handle.net/2123/27902.
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The liver has a key role both from a metabolic and an immunological viewpoint. It is involved in the metabolism, or degradation of different molecules absorbed by the intestine, including xenobiotics, drugs and lipids, the synthesis and turnover of plasma proteins, the production of bile and the storage of glycogen and vitamin A. Unique amongst solid organs, the sinusoidal endothelium of the liver is perforated with pores, or fenestrations,
and is not separated from hepatocytes by a basal lamina. It has been proposed that the fenestrations, also termed the ’liver sieve’, function as a bio-filter allowing free diffusion of small molecules (less than 100 nm in diameter) from the blood to the hepatocytes and Vice versa. Changes in these structures, as seen in ageing, could have important effects on hepatic function and in particular lipid metabolism.
The liver also has unique immunological functions including T-cell
activation and tolerance. This thesis explores potential new roles of the
fenestrated sinusoidal endothelium in some aspects of liver immunology and
ageing.
6
Bird, Thomas Graham. "Liver regeneration by hepatic progenitor cells". Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5634.
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The liver is the largest solid organ in the body and is frequently the site of injury. During disease, liver injury is usually compensated for by exceptionally efficient regeneration which occurs both from differentiated epithelia and also from an undifferentiated cell population with stem cell like qualities known as hepatic progenitor cells (HPCs). HPCs are particularly active during massive or chronic liver injury and therefore are an attractive target for much needed novel therapies to enhance regeneration in patients for whom the only current effective therapy is liver transplantation. Stem cells in other organs systems are believed to reside in a specialised microenvironment or niche which supports their maintenance and function. To investigate the hypothesis that HPCs are supported by a functional niche and are capable of regenerating hepatocytes, we commenced by establishing a number of murine in vivo models. Having shown a stereotypical niche, consisting of macrophages, myofibroblasts and laminin exists in both animal models and human disease, we investigated the active recruitment of extrahepatic cells into this niche and showed that macrophages are actively recruited from the bone marrow during liver injury. Macrophages were shown to influence HPC behaviour during injury. Furthermore using macrophages as a cellular therapy, induced HPC activation with corresponding changes to liver structure and function. Investigation of signalling pathways revealed and confirmed a TWEAK dependent activation of HPCs following macrophage transfer. Having demonstrated the potential for macrophage therapy via HPC activation, we aimed to study the ability of HPCs to regenerate the hepatic parenchyma. To do so we developed and characterised a novel model of hepatocellular injury and HPC activation. Using the genetic labeling of hepatocytes in this model we were able to show rapid and large scale repopulation of hepatocytes from a precursor source with HPCs being the critical precursor source of hepatocellular regeneration. In addition this process is again dependent on TWEAK signalling, without which HPC mediated regeneration fails resulting in mortality. Therefore HPCs are an attractive biological target for regenerative medicine, and both TWEAK signalling and autologous macrophage infusion offer genuine potential to manipulate these cells as future therapies.
7
Cheluvappa, Rajkumar. "Pathophysiology of Liver Sinusoidal Endothelial Cells". Thesis, The University of Sydney, 2008. http://hdl.handle.net/2123/2802.
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Owing to its strategic position in the liver sinusoid, pathologic and morphologic alterations of the Liver Sinusoidal Endothelial Cell (LSEC) have far-reaching repercussions for the whole liver and systemic metabolism. LSECs are perforated with fenestrations, which are pores that facilitate the transfer of lipoproteins and macromolecules between blood and hepatocytes. Loss of LSEC porosity is termed defenestration, which can result from loss of fenestrations and/ or decreases in fenestration diameter. Gram negative bacterial endotoxin (Lipopolysaccharide, LPS) has marked effects on LSEC morphology, including induction LSEC defenestration. Sepsis is associated with hyperlipidemia, and proposed mechanisms include inhibition of tissue lipoprotein lipase and increased triglyceride production by the liver. The LSEC has an increasingly recognized role in hyperlipidemia. Conditions associated with reduced numbers of fenestrations such as ageing and bacterial infections are associated with impaired lipoprotein and chylomicron remnant uptake by the liver and consequent hyperlipidemia. Given the role of the LSEC in liver allograft rejection and hyperlipidemia, changes in the LSEC induced by LPS may have significant clinical implications. In this thesis, the following major hypotheses are explored: 1. The Pseudomonas aeruginosa toxin pyocyanin induces defenestration of the LSEC both in vitro and in vivo 2. The effects of pyocyanin on the LSEC are mediated by oxidative stress 3. Defenestration induced by old age and poloxamer 407 causes intrahepatocytic hypoxia and upregulation of hypoxia-related responses 4. Defenestration of the LSEC seen in old age can be exacerbated by diabetes mellitus and prevented or ameliorated by caloric restriction commencing early in life
8
Cheluvappa, Rajkumar. "Pathophysiology of Liver Sinusoidal Endothelial Cells". University of Sydney, 2008. http://hdl.handle.net/2123/2802.
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Doctor of Philosophy(PhD)Owing to its strategic position in the liver sinusoid, pathologic and morphologic alterations of the Liver Sinusoidal Endothelial Cell (LSEC) have far-reaching repercussions for the whole liver and systemic metabolism. LSECs are perforated with fenestrations, which are pores that facilitate the transfer of lipoproteins and macromolecules between blood and hepatocytes. Loss of LSEC porosity is termed defenestration, which can result from loss of fenestrations and/ or decreases in fenestration diameter. Gram negative bacterial endotoxin (Lipopolysaccharide, LPS) has marked effects on LSEC morphology, including induction LSEC defenestration. Sepsis is associated with hyperlipidemia, and proposed mechanisms include inhibition of tissue lipoprotein lipase and increased triglyceride production by the liver. The LSEC has an increasingly recognized role in hyperlipidemia. Conditions associated with reduced numbers of fenestrations such as ageing and bacterial infections are associated with impaired lipoprotein and chylomicron remnant uptake by the liver and consequent hyperlipidemia. Given the role of the LSEC in liver allograft rejection and hyperlipidemia, changes in the LSEC induced by LPS may have significant clinical implications. In this thesis, the following major hypotheses are explored: 1. The Pseudomonas aeruginosa toxin pyocyanin induces defenestration of the LSEC both in vitro and in vivo 2. The effects of pyocyanin on the LSEC are mediated by oxidative stress 3. Defenestration induced by old age and poloxamer 407 causes intrahepatocytic hypoxia and upregulation of hypoxia-related responses 4. Defenestration of the LSEC seen in old age can be exacerbated by diabetes mellitus and prevented or ameliorated by caloric restriction commencing early in life
9
Ma, Kwai-yee Stephanie. "Identification and characterization of tumorigenic liver cancer stem/progenitor cells". Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39557534.
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Poli, G. "Biochemical studies on CC14̲-induced liver injury using isolated rat liver cells". Thesis, Brunel University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379250.
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Ma, Kwai-yee Stephanie, i 馬桂宜. "Identification and characterization of tumorigenic liver cancer stem/progenitor cells". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557534.
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Li Ka Shing Prizes for best PhD theses in the Faculties of Dentistry, Engineering, Medicine and Science, 2006-2007published_or_final_version
abstract
Pathology
Doctoral
Doctor of Philosophy
12
Lam, Shuk-pik, i 林淑碧. "Differentiation of mesenchymal stem cells (MSCs) into hepatocytes in acute liver injury". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43085647.
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Chan, Kwok-kin, i 陳國堅. "In vivo study on cell cycle and checkpoint regulation during mouse liver development". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B4559000X.
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14
Kung, Janet Wui Cheung. "Investigating the liver progenitor cell niche in the developing human liver". Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25953.
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Liver cirrhosis places an increasing burden on healthcare worldwide. Currently the only treatment is liver transplantation. Whilst liver transplant has a relatively good five-year survival, donor organ shortage costs many lives every year and results in lifelong immunosuppression. Alternative treatments are thus urgently needed. It is with this background that there is understandable interest for the development of stem cell therapies for liver regeneration. The identification of putative liver stem cells has brought closer the previously separate fields of liver ontology, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bio-artificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers. Human liver progenitor cells (LPCs) have therapeutic potential but their in vitro culture results in inadequate differentiation, function, and phenotypic instability reflecting an incomplete understanding of in vivo processes. LPCs can be robustly isolated from second trimester human foetal livers by immunoselection for EpCAM+/CD29+/CD49d+/CD49e–/CD235a–/CD45– cells. Expression profiling of mRNA and microRNA in human foetal LPCs was performed and compared with mature human hepatocytes and human embryonic stem cells undergoing hepatocytic differentiation. Foetal LPCs exhibit a distinct transcriptome profile consistent with a stem cell signature, cell division, and some liver-specific functions. Bioinformatic integration of microRNA and mRNA datasets revealed that microRNAs up-regulated in LPCs targeted genes involved in metabolic processes implying repression of the mature hepatocyte phenotype. Control of LPC gene expression therefore occurs at both transcriptional and, via microRNAs, post-transcriptional levels. Furthermore, transcription factor binding site analyses revealed enriched E2F1 motif in gene and microRNA promoters suggesting feedback control in determining LPC fate. Foetal LPCs were capable of differentiation to a hepatocytic phenotype in the presence of appropriate paracrine signals provided by EpCAM– non-parenchymal cells (NPCs), which consist mainly of endothelial cells and hepatic stellate cells. Fibronectin, despite being produced in abundance by EpCAM– NPCs, had no effect on LPC synthetic function in vitro. The expression of fibronectin in the perisinusoidal space suggests its potential role of modulating cross-talk between hepatoblasts/hepatocytes, liver sinusoidal endothelial cells, and hepatic stellate cells. Fibronectin expression in the portal vein mesenchyme and laminin α5 expression along the ductal plate suggest that both matrix molecules, located in close proximity to LPCs, may be important in supporting the LPC niche. Findings in this work provide insight into the regulation of the human foetal LPC functional phenotype, bringing stem cell-based therapies for liver disease one step closer.
15
Amofah, Eunice. "Bone marrow stem cells in liver disease". Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497234.
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Lee, Matthew L., i Jonathan M. Peterson. "Ethanol Disrupts Metabolic Signaling in Liver Cells". Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/69.
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Alcohol abuse is the third leading cause of preventable death in the United States. Excessive intake of alcohol can result to alcoholic fatty liver disease, the number one cause of live related mortalities in the US. The outlining purpose for this project is to determine the alcohol-induced changes in the liver cell protein signaling. For this project, we treated H4IIE rat hepatoma cells (with 100 and 200 mM ethanol overnight). H4IIE cells were chosen because they are a commonly used liver cell culture line that maintains characteristics of intact liver cells. After treatment we collected and prepared the cells for protein signaling analysis, using standard western blotting procedure. A western blot detects relative quantity of proteins in a sample. Briefly, protein samples are separated by size through electrophoresis, smaller proteins move faster through the gel so that the larger proteins are toward the top and smaller towards the bottom. The proteins are then transferred to a nitrocellulose membrane and protein concentration is detected by chemiluminescence. We chose to examine the effects of ethanol on the activation of the key regulator of metabolic signaling, Protein Kinase B/Akt (Akt). Based on our results, ethanol has no effect on the total amount of Akt in the H4IIE liver cells. However, ethanol significantly attenuates insulin-induced activation of Akt in a dose-dependent manner, as seen by a reduction in the amount of phosphorylated Akt. Therefore, we conclude that treatments that increase Akt activation may be a viable option for the treatment of alcoholic fatty liver disease.
17
Viebahn, Cornelia Sabine. "Interaction between the immune system and liver progenitor cells". University of Western Australia. Biochemistry and Molecular Biology Discipline Group, 2009. http://theses.library.uwa.edu.au/adt-WU2010.0055.
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Liver progenitor cells (LPCs) play a major role in the regeneration process following chronic liver damage. LPCs can differentiate into hepatocytes and cholangiocytes and thus are capable of replenishing the damaged liver. Due to their plasticity and robust nature in culture systems, they are promising candidates for use in cell therapy. However, to be able to use LPCs as tissue regenerating stem cell-like cells in the clinic, we need to fully understand how they are controlled. Although a strong association between LPCs and inflammation has been shown in many chronic liver diseases, the role of the immune system in LPC-mediated hepatic regeneration is poorly understood. We hypothesise that specific immune cells and mediators are needed to induce the LPC compartment, and that these are common to the LPC response in different injury settings. Therefore, the present study focused on the characterisation of the inflammatory environment in the LPC response, which generates this niche. The aims of this study were (i) to identify the immune cells that are important for the LPC response, (ii) to define the cytokine profile and (iii) to determine the role of the cytokine producing cells during liver regeneration. To study hepatic inflammation following liver injury, a diet-induced model of liver injury (choline-deficient, ethionine-supplemented diet, CDE diet) was compared to two transgenic mouse models of immune-mediated hepatitis (Met-Kb, 178.3). Although all three models are characterised by hepatitis, histological analysis revealed that LPCs were only detectable in the CDE and Met-Kb livers. In the 178.3 model, livers regenerated from proliferating hepatocytes. An LPC response could not be induced in these mice even when liver damage was made more severe. In the other two models, LPC numbers increased over time showing the highest numbers one week after the peak of liver injury. LPCs were often found in close proximity to inflammatory cells, in particular macrophages.
18
Endo, Kosuke. "Pretransplant replacement of donor liver grafts with recipient Kupffer cells attenuates liver graft rejection in rats". Kyoto University, 2015. http://hdl.handle.net/2433/199205.
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Cowie, David. "Differential induction of organic anion transporting polypeptides in rat liver". Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources. Restricted: no access until April 24, 2020, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=25707.
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20
Anilkumar, Thapasimuthu Vijayamma. "The pathobiology of hepatic stem cells (oval cells)". Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244072.
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21
Akingbasote, J. A. "The potential role of liver sinusoidal endothelial cells in drug-induced liver injury". Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3005113/.
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Liver sinusoidal endothelial cells (LSEC) constitute a unique population of endothelial cells with specialised liver-specific morphologic features and functions. LSEC are the only endothelial cells with fenestrations and which lack an organised basement membrane. They are involved in hepatic stellate cell (HSC) quiescence, endocytosis of small particles, selective transfer of substances from the blood, in the hepatic sinusoid, to the parenchymal cells and in liver regeneration. As the group of cells that form the inner lining of the capillaries of the liver sinusoids, and being the first to be in contact with blood-borne particles, pathogens, and xenobiotics, they are prone to the deleterious effects of these. The aims of this thesis were to investigate the unique features of human liver sinusoidal endothelial cells (HLSEC) in comparison with endothelial cells from other vascular beds, evaluate the sensitivities of HLSEC to a range of hepatotoxic drugs, including small-molecule receptor tyrosine kinase inhibitors (RTKIs), such as regorafenib, and to explore the role of HLSEC in a triculture human liver microtissue. Results obtained from this study showed that HLSEC expressed phenotypic features of vascular and lymphatic endothelial cells, particularly vascular endothelial growth factor receptor 2 (VEGFR-2) which could be activated by VEGF-A to stimulate cell proliferation, migration and tubular morphogenesis. HLSEC also expressed functional VEGFR-3. Transcriptomic analysis indicated that HLSEC expressed specialised genes, such as plasmalemma vesicle associated protein (PLVAP), that support its liver-specific structure and functions. HLSEC were more sensitive to a range of small-molecule receptor tyrosine kinase inhibitors than other hepatic cells. (primary human hepatocytes [PHH] and human hepatic fibroblasts [HHF]) and endothelial cells from other vascular beds (human dermal microvascular endothelial cells and human dermal lymphatic endothelial cells). Regorafenib inhibited the activation of VEGFR-2 thereby abrogating cell proliferation, migration, tubular morphogenesis as well as upregulation of angiocrine factors involved in liver regeneration following activation by vascular endothelial growth factor A (VEGF-A). Regorafenib also caused a disruption of cytoskeletal structure of HLSEC and induced apoptosis via activation of caspase 3. Triculture liver microtissues formed with PHH, HLSEC and HHF were vascularised with higher expression of liver-specific drug-metabolising enzymes in comparison with the same combination of cells cultured as a monolayer. However, metabolic competence of triculture liver microtissues was significantly lower than in their monoculture counterparts (consisting of PHH only). This study has further confirmed the uniqueness of HLSEC as a specialised endothelial cell adapted to its anatomical role, which could respond to a range growth factors to initiate endothelial cell-specific functions. It has also been demonstrated that HLSEC are a direct target of hepatotoxic drugs. Triculture liver microtissues generated with PHH, HLSEC and HHF showed less metabolic competence than their PHH-only counterparts. Future studies need to investigate the role of RTKIs in vascular toxicity using in vivo models of sinusoidal obstruction syndrome (SOS) and liver regeneration. Finally, it would be informative to investigate the possibility of identifying HLSEC-specific biomarkers of liver toxicity.
22
Lam, Shi. "The significance of hepatic stellate cell activation in small-for-size fatty liver graft injury /". View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B3829686X.
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Gow, Adam George. "Production of canine hepatocyte-like cells from stem cell sources". Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/10057.
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The cost of drug development is high with many drugs failing during toxicity testing. This is a particular problem in veterinary medicine where the pharmaceutical market size is so small that it may not be economically viable to develop drugs. The liver and specifically hepatocytes have a crucial role in drug metabolism via oxidation by cytochrome enzymes (CYP), conjugation and excretion into the biliary system. This drug metabolism is unpredictable between species as each has unique CYP profiles. Furthermore there is breed variation of CYP profiles within the canine species. The ability to produce an in vitro source of canine hepatocytes to model drug metabolism in this species and in different breeds would greatly reduce the expense of candidate drug testing. If an unlimited supply could be produced in vitro this would reduce the number of animals required in pre-clinical testing. The aim of this thesis was to produce an in vitro supply of canine hepatocyte-like cells from stem cell sources, namely hepatic progenitor cells (HPC), mesenchymal stem cells (MSC) or induced pluripotent stem cells (iPSC). Cultures of canine primary hepatocytes were produced to use as a gold standard, but also to develop and refine tests of hepatocyte characterisation and function. A panel of primers was developed for use in real time polymerase chain reaction (PCR) as well as optimising tests for low density lipoprotein (LDL) and indocyanine green uptake, albumin production, periodic acid- Schiff staining for glycogen and CYP activity using a luciferase-based system. As primary hepatocytes rapidly lost their defining characteristics and function in vitro, methods of maintaining function using CYP inducers and culture substrates were assessed. Isodensity centrifugation and magnetic-activated cell sorting was employed to isolate HPCs. Selection of cells from the non-parenchymal cell fraction with stem cell marker Prominin 1 demonstrated that these were keratin 7 positive, a HPC marker. Cells morphologically consistent with HPC appeared and expanded in culture after 2 weeks. On passaging, these cells failed to continue expanding, despite plating onto collagen, laminin, SNL feeder cells or using Kubota’s medium (known to allow rapid expansion of rodent and human HPCs). Canine adipose (Ad-MSC) and bone marrow-derived mesenchymal stromal cells (BM-MSC) were isolated post mortem. These were characterised as CD45, 105 and STRO-1 positive, CD11b, 19 and 45 negative cells which could be differentiated into adipocytes, chondrocytes and osteocytes based on staining characteristics and relative gene expression. Protocols published for other species were used to differentiate both Ad-MSC and BM-MSC towards a hepatocyte phenotype. Although a dramatic change in morphology and a reduction in vimentin gene expression were noted, suggesting a loss of mesenchymal phenotype, these protocols did not induce a hepatocyte phenotype. Pre-treatment with 5-Aza-2′-deoxycytidine to cause DNA demethylation and valproic acid to inhibit histone deacetylation also failed to allow transdifferentiation. A polycistronic vector containing Oct-4, c-Myc, Sox2 and Klf4 was successfully transfected into canine epidermal keratinocyte progenitor cells which became alkaline phosphatase positive and assumed a morphology consistent with iPSC. After colony selection and expansion, PCR evidence of plasmid presence was lost, colony morphology changed, and alkaline phosphatase activity reduced, consistent with vector expression factor and pluripotency loss. Canine iPSCs produced by lentiviral method were then differentiated towards hepatocyte phenotype using a published protocol for mouse and human iPSC. These cells were then assessed for hepatocyte characteristics using the developed reagents and primers. These cells demonstrated increased gene expression and morphology consistent with differentiation towards a hepatocyte-like phenotype. This thesis demonstrates successful culture of canine primary hepatocytes and validation of tests of hepatocyte phenotype. This provides a basis for optimising primary hepatocyte function in vitro and assessment of the success of differentiation protocols on stem cell sources. Canine mesenchymal stromal cells do not appear to transdifferentiate towards a hepatocyte-like phenotype using published protocols for other species. Canine iPSC are a promising candidate for an in-vitro source of hepatocyte-like cells.
24
Kita, Sadahiko. "The protective effect of transplanted liver cells into the mesentery on the rescue of acute liver failure after massive hepatectomy". Kyoto University, 2016. http://hdl.handle.net/2433/216179.
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出版日2016/2/15を明示する必要あり。発行号・ページ数が決まっていればそれらも明示する必要あり。 Final publication is available at http://dx.doi.org/10.3727/096368916X690999Kyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第19925号
医博第4145号
新制||医||1017(附属図書館)
33011
京都大学大学院医学研究科医学専攻
(主査)教授 長船 健二, 教授 伊達 洋至, 教授 坂井 義治
学位規則第4条第1項該当
25
Aravinthan, Aloysious Dominic. "Hepatocyte senescence in chronic liver disease". Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708050.
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Köhn, Julia. "Characterisation of liver progenitor cells and their microenvironment during chronic liver disease and hepatocarcinogenesis". Thesis, Curtin University, 2016. http://hdl.handle.net/20.500.11937/48824.
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The studies in this thesis aimed to characterise liver progenitor cells and their microenvironment during chronic liver injury conditions. A comprehensive comparison of the two common murine chronic liver disease models, CDE versus TAA, was performed. Parameters such as hepatocyte health, inflammation, fibrosis and the LPC response were investigated during stages of injury induction, establishment, maintenance, progression and carcinogenesis. Furthermore, the relationship between LPCs and HCC development in humans was investigated in a retrospective study.
27
Aoi, Takashi. "Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells". Kyoto University, 2008. http://hdl.handle.net/2433/124215.
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Dong, Xin Min. "HCV-Core over-expressed specifically in liver cells". Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27834.
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Hepatitis C viruses (HCV) affect 170 million patients, but only a minority of patients develop symptoms and manage to clear the virus, and the pathogenesis remains unknown. Previous studies discovered that some viral proteins may suppress HCV specific T lymphocytes, leading to lower immune responses. Although many mouse models have been tried in laboratories worldwide, none of them mimicked natural Human HCV infection with individual HCV genes in vivo.
To study the immunopathogenesis of HCV infections, we constructed some chimeric liver-specific vectors and one was selected to establish promoted mouse models, which express individual HCV genes specifically in the liver. In this research, the over-expression of HCV-Core and the cellular immune responses in mice driven by global and liver-specific promoters were also detected. Although the DNA injection needs to be optimized, our results indicate that liver-specific expression may provide a new way to elucidate the pathogenesis of HCV infections.
29
Demirkiran, Ahmet. "Dynamics of regulatory T cells in liver transplantation". [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10694.
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Nobes, Catherine Diane. "The control of respiration of isolated liver cells". Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316770.
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Pandolfi, Vittoria. "Microencapsulation of hepatic cells for extracorporeal liver supply". Thesis, Compiègne, 2016. http://www.theses.fr/2016COMP2262/document.
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Aujourd’hui, la transplantation est le seul traitement efficace proposé aux patients souffrant d’une insuffisance hépatique fulminante. La nécessité de disposer d’un système de suppléance hépatique transitoire apparaît donc indispensable. C’est dans cet axe que se sont développés les systèmes qualifiés de foies bio artificiels (BAL). Leur principale caractéristique est d’incorporer un bioréacteur hébergeant des cellules pouvant restaurer l’activité hépatiques dans son ensemble. A l’heure actuelle, les hépatocytes primaire humains (HEP) issus de foies de donneurs non transplantables sont considérées comme le meilleur choix. Cependant, leur utilisation reste limitée par leur faible disponibilité et la difficulté à les maintenir différenciés en culture in vitro. Pour remédier à ce dernier point, l’approche la plus prometteuse semble être une co-culture des hépatocytes avec les cellules non parenchymateuses afin de recréer un environnement proche des sinusoïdes hépatiques. Ce travail de thèse repose sur la mise en place d’une nouvelle approche de co-culture tridimensionnelle sous la forme de sphéroïdes, d’HEP primaires avec les principaux types de cellules non-parenchymateuses (les cellules de Kupffer, les cellules endothéliales et les cellules étoilées) selon des proportions spécifiques. Puis de leurs encapsulations dans des billes d’alginate et leurs cultures au sein d’un bioréacteur à lit fluidisé. Ce modèle s’est révélé pertinent et approprié à maintenir les fonctions hépatiques dans le temps. Bien que beaucoup d’optimisation reste à définir, ce travail exploratoire témoigne de l’intérêt de cette approche intéressante pour le progrès des systèmes BALLiver shortage makes transplantation inapplicable to all acute liver failure patients. Bioartificial Iiver (BAL) devices represent a temporary solution for these patients which are thereby bridged tilt Iiver transplantation or regeneration BAL treatment offers blood purification and substitution of metabolic functions through the activity of hepatocytes (HEPs), which are integrated in the device within acclimating containers, so-called bioreactors. Primary human hepatocytes are the ideal cell type to use in BAL, but they are scarcely available and difficult to maintain in vitro. Co-culture of HEPs with supporting cells has been proposed as the most promising strategy for preserving HEP behaviors in in vitro conditions. In fact, assisting cells types hold their ability to influence functional responses of the HEPs by providing them with cues of the native organ.This PhD work proposed a novel approach of co-culture for the functional sustain and preservation of the HEPs in the environment of the fluidized bed bioreactor (designed in our Iaboratory). Definition of this model took inspiration from the cellular organization in the organ; therefore, it employed three major sinusoidal non-parenchymal cell populations (liver sinusoidal, Kupffer, and hepatic stellate cells) which, together with HEPs, were cultured with three-dimensional arrangement (spheroids) and according to specific proportions. The resulting model was characterized in terms of functional benefits for the HEPs, and then applied in the microenvironment of alginate beads, which provide cells with immunological and mechanical protection in the fluidized bed bioreactor. This spheroidal multi-cultured model revealed its potentiality in sustaining in vitro HEP behaviors over time. Although much remains to be refined, this model may represent an interesting approach for the progress of BAL
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CROCE, STEFANIA. "Mesenchymal stromal cells on bioscaffold for liver bioengineering". Doctoral thesis, Università degli studi di Pavia, 2020. http://hdl.handle.net/11571/1329186.
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Tissue bioengineering is the creation of functional tissues or whole organs by manufacturing body parts ex vivo, seeding cells on a supporting scaffold. The final goal of organ bioengineering is the use of the bioengineered organs as ‘replacement parts’ for the human body. The need for bioengineered livers is significant: currently, the only effective treatment for end-stage liver failure is orthotopic liver transplantation. However, the shortage of organ donors results every year in the death of many patients in the waiting list. Moreover, the advantage of this technology is the use of autologous cells that eliminates the need for post-transplant immunosuppression.
In the present study, we decellularized pig livers and then repopulated them with allogeneic porcine mesenchymal stromal cells (pMSCs) to study the interaction between pMSCs and liver specific ECM. The final aim was to understand if ECM can influence and/or promote pMSCs toward differentiation into hepatocytes or hepatocyte-like cells without specific growth factor in culture medium.
In our experimental project, porcine livers were obtained by a surgical technique similar to the one used for explant in a human cadaveric donor. Liver samples were cut and then decellularized through agitation with 0.15% SDS. The quality of the decellularization was evaluated both qualitatively and quantitatively, with histological staining and DNA quantification respectively. pMSCs were isolated from the porcine bone marrow (BM) and expanded in vitro. pMSC were characterized by assessment of morphology, proliferation capacity, immunophenotype and their differentiation ability. Then, pMSCs were used for seeding the scaffolds with static culture method. The repopulation of the recellularized scaffold was evaluated at 3, 7, 14 and 21 days after seeding with H&E stain, DAPI, MTT assay and SEM analysis, showing an increase in the cell number with increasing culture days. In order to determinate whether culture on liver ECM-scaffold could promote/address differentiation of pMSC towards hepatocyte, the transcriptional levels of some hepatic genes were tested. In particular, we evaluated six genes (ALB, AFP, HNF4a, Cyp1a1, Cyp7a1 and Krt18) associated to different phases of the hepatic development. A comparison with the expression profile was made with both porcine primary hepatocyte and pMSC.
The observations obtained so far allow us to state that: i) our decellularization protocol is effective in the removal of the cells from native liver, respecting the parameters for decellularization without damage the structure of ECM; ii) pMSCs obtained from porcine BM have characteristic phenotypically and functionally comparable to those of their human counterparts and therefore they can be used as a model for experimental studies such as for liver ECM recellularization; iii) the static seeding strategy of pMSCs on the scaffold resulted to be effective in terms of ECM cell attachment, cell proliferation and migration inside the specimen, iv) the genic profile of cells seeded on ECM scaffold without any growth factors is more similar to pMSC suggesting that the only contact with liver specific ECM is not strong enough to induce a complete differentiation in HLCs. Despite this, we observed that Cyp7a1 gene, expressed in hepatocyte but not in MSC, was present in pMSC seeded scaffolds at each time points.
In conclusion, we can observe that our results are in accordance with data reported in literature and sustain the possibility to use decellularizated organs as biological scaffold to create functional organs. We believe that our results may provide new insights toward a better understanding of early HLCs development on ECM-scaffolds. However, a more detailed decellularization process, a better cell differentiation capacity and a more detailed understanding of the interaction between cells and ECM could represent crucial steps in the progression of this research field.
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呂可欣 i Ho-yan Lui. "Effects of lipoic acid on oxidant-induced cytotoxicity in HepG2 cells". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31969768.
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Lui, Ho-yan. "Effects of lipoic acid on oxidant-induced cytotoxicity in HepG2 cells". Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2203240X.
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O'Neill, Kathy. "Reprogramming hepatocytes into duct-like cells". Thesis, University of Bath, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528369.
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Primary hepatocytes maintained in culture progressively down regulate liver-specific genes and lose their characteristic function and morphology. This process, termed dedifferentiation, is a hindrance to in vitro modelling of systems such as xenobiotic metabolism, liver disease and regeneration. However the results presented here demonstrate that dedifferentiated hapatocytes spontaneously induce expression of ductal genes, and therefore represent a useful model of cell reprogramming.
36
Ling, Changchun, i 凌长春. "The role of graft injury in mobilization of endothelial progenitor cells, myeloid derived suppressor cells and regulatory T cells afterlive transplantation". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47849769.
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Liver transplantation is the best therapy for patients with end-stage liver diseases and unresectable early hepatocellular carcinoma (HCC). Living donor liver transplantation (LDLT) has been successfully implemented as an alternative to deceased donor liver transplantation (DDLT) and likewise offers comparable excellent survival rate. However, the inferior post-transplant oncological outcomes are found in LDLT recipients with HCC. The liver grafts used in LDLT are usually small-for-size and less effective in coping with shear stress from transient portal hypertension, which results in small-for-size liver graft injury. Acute phase small-for-size liver graft injury may promote late phase tumor recurrence, whereas the underlying mechanism remains unclear.
CXCL10, an inflammatory chemokine, initiates liver inflammatory response during hepatic ischemia-reperfusion (IR) injury and may link acute phase small-for-size liver graft injury and late phase tumor recurrence, yet the precise mechanisms remain elusive. Endothelial progenitor cells (EPCs) participate in tissue repair for graft recovery and also provide an angiogenic environment for tumor growth. Myeloid derived suppressor cells (MDSCs) and regulatory T cells (Tregs) can suppress the activation of the immune system and play a critical role in graft rejection and cancer development.
We here established the rat orthotopic liver transplantation with whole graft or small-for-size graft model to study the impact of acute phase small-for-size liver graft injury on the mobilization of EPCs, MDSCs and Tregs, and intragraft CXCL10 and its receptor, CXCR3,gene expressions. We further subjected CXCL10-/-mice and CXCR3-/-mice to hepatic IR injury and major hepatectomy to study the role of CXCL10/CXCR3 signaling on the mobilization of EPCs, MDSCs and Tregs. We also investigated the effect of CXCL10 on EPC migration and tube formation in vitroas well as intratumoral microvessel density (MVD) in the rat liver transplantation with tumor growth model and EPCs on tumor growth in nude mice.
Key findings:
1. Liver transplantation with small-for-size graft resulted in severe intragraft vascular injury and higher CXCL10 andCXCR3 gene expressions as well as more EPC, MDSC and Treg cell mobilizationin circulation than whole graft.
2. CXCL10-/-mice and CXCR3-/-mice had less circulating EPCs, MDSCs and Tregs than WT mice after hepatic IR injury and major hepatectomy.
3. CXCL10 recruited EPCs in dose-dependent and CXCR3-dependent manners and promoted EPC tube formation in vitro.
4. Higher intratumoral MVD was observed in small-for-size graft than in whole graft in liver transplantation with tumor growth model.
5. Tumor grew more quickly by combining EPC infusionin nude mouse orthotopic liver tumor model.
In conclusion, acute phase small-for-size liver graft injury significantly mobilizes EPCs, MDSCs and Tregs after transplantation through CXCL10/CXCR3 signaling. More EPC mobilization and intragraft differentiation after transplantation with small-for-size liver graft may be related to higher intratumoral MVD in small-for-size liver graft after transplantation with tumor development. Therefore, targeting at post-transplant CXCL10/CXCR3 signaling may not only attenuate early phase liver graft injury but also prevent late phase tumor recurrence.published_or_final_version
Surgery
Doctoral
Doctor of Philosophy
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Ge, Xupeng. "Mechanisms of liver allograft rejections /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-330-2/.
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Chandrasekaran, Prakash Gerber David A. "Encapsulation of hepatic progenitor cells for liver tissue engineering". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,963.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Dec. 18, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biomedical Engineering." Discipline: Biomedical Engineering; Department/School: Medicine.
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Al, Echrish Noori H. Jasim. "Liver development and the role of mesenchymal stem cells". Thesis, University of Nottingham, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.580160.
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Human fetal liver is the major site of haematopoiesis throughout gestation but at around 12 - 13, weeks hepatogenesis becomes prominent. In the first trimester, the fetal liver contains a number of putative stem cell populations in microenvironmental niches. This study was designed to investigate these stem cell populations to determine the origins of hepatogenesis in fetal life and to determine the implications for hepatic regeneration in adults. Mesenchymal stem cells were isolated from fetal liver samples (fIMSC) on the basis of adherence to tissue culture plastic. The phenotype of the adherent population, using flow cytometry was determined as: CD29+ve, CD10S+ve, CD90+ve, CD73+ve, HLA ABC+ve, CD271-ve, CD4S-ve, CD34-ve, CD133-ve, CDllb-ve & HLA DR-ve. Differentiation of flMSC into osteogenic, adipogenic and chondrogenic lineages was also demonstrated as confirmation of the multipotential nature of these cells. Cells which were expanded clonally showed the same characteristics as the primary cell population. Thus, MSC isolated from human fetal liver conformed to criteria stipulated by International Society of Cellular Therapy (ISCT). flMSC were extensively passaged in vitro to relatively large passage numbers (P1S). It was observed that there was a reduction in expression of CD10S associated with a decrease in proliferative and differentiation properties of the cells. These findings appeared to be associated with chromosomal abnormalities and a shortening of telomere length over increasing passage number, which could be considered as a triggering of cell senescence. It was concluded that the early passage numbers of flMSC (P4-P8) are optimum for all studies and that CDi0S is a reliable and accessible surrogate marker for identification of senescent cells. flMSC were cultured in proprietary medium, supplemented with growth factors which are known to stimulate hepatogenesis. A greater degree of hepatogenesis from flMSC was observed when the medium was supplemented with oncostatin M (OSM), in comparison to culture in a medium supplemented with fibroblast growth factor (FGF) or hepatocyte growth factor (HGF). A hepatocyte-specific antibody and gene profiling were used to analyse the development of flMSC in these culture conditions. Hepatic cluster formation (indocyanine green positive) was noted within 3 days when flMSC cultured in the presence of FGF. Then after subsequent adding of OSM, cultured flMSC stained positively by flow cytometric analysis using an optimised hepatocyte-specific antibody and gene expression studies confirmed the presence of albumin, alpha-fetoprotein, factor VIII and tryptophan 2,3 dioxygenase in these cells. The cells acquired a polygonal morphology, similar to that of adult hepatocytes. The flMSC characterised in this study were shown to possess immunomodulatory activity: they do not induce aT-cell response and they have an immunosuppressive effect on T-cells in mixed Iymphocyte culture. flMSC differentiated to hepatocytes have the same immunological properties as undifferentiated fIMSC, despite expression of HLA DR when the cells are exposed to pro-inflammatory cytokines. This study shows that human fetal liver-derived MSC can develop into functional hepatocytes in vitro and that these end-stage cells have immunomodulatory properties. This de novo source of hepatic tissue could have therapeutic utility with potential for transplantation across HLA barriers.
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Lu, Wei-Yu. "Defining the liver repopulating capacities of hepatic progenitor cells". Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17875.
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The liver has the ability to regenerate rapidly during acute liver injury by activating mature hepatocytes to divide and restore the damaged liver mass. In contrast, the liver relies on hepatic progenitor cells (HPCs) which have the ability to differentiate into both hepatocytes and biliary cells for regeneration during chronic liver injuries. Whole organ transplant is the most effective treatment for end stage liver diseases. However, there is a constant shortage of donor organs causing the death of many patients while waiting for suitable donor organs. HPC transplant is a potential alternative for whole organ transplant. However the isolation of HPC which is scarce in the liver and the expansion of these cells to a number that is suitable for transplant have been challenging. To investigate the plausibility of using HPCs as an alternative for liver transplant, I developed a protocol to isolate and expand HPC in vitro. Using this system, I investigated the complex hierarchy of HPCs in aid to select a defined population of HPC that is suitable for transplant. I found the EpCAM+ CD24+ population marks a naïve population of HPC that might be suitable for cell therapy. I further investigate the liver repopulating capacities of these cells by isolating EpCAM+CD24+ HPC population by Fluorescence Activated Cell Sorting (FACS) from a hepatocellular injury model. Surprisingly, a subpopulation of the EpCAM+ CD24+ HPCs which are also CD133+ possesses a higher colony forming capacities has been identified. Most importantly, this population can be expanded to a large scale in vitro and able to repopulate the injured liver after transplant. This defined population of HPCs can also be isolated from a mouse model of fatty liver disease and the isolated HPCs can be expanded in vitro. These cells are able to repopulate the liver after cell transplantation. The presence of HPCs that are capable of being isolated from the fatty liver proved the potential of using HPCs for transplant in a clinical setting by using cells isolated human fatty liver that are from rejected for transplant to overcome the shortage of donor organs.
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Tostões, Rui Manuel Lucas Gameiro Domingues. "Process engineering of liver cells for drug testing applications". Doctoral thesis, Faculdade de Ciências e Tecnologia, 2012. http://hdl.handle.net/10362/7612.
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Dissertação para obtenção do Grau de Doutor em
BioengenhariaThe primary culture of human hepatocytes is a requirement in drug development tests. This application is currently hampered by two problems: the limited proliferation of the hepatocytes and the rapid loss of liver-specific phenotype of these cells, when cultured in vitro. This thesis aimed at minimizing this latter issue by cultivating hepatocytes, as spheroids, in fully controlled bioreactors. The state of the art of the primary cultures of hepatocytes is reviewed in Chapter 1, after a brief introduction to the liver physiology the drug development process. The improvement of the bioreactor cultures of hepatocyte spheroids was initially done using freshly isolated rat hepatocytes; the effects of alginate microencapsulation, perfusion culture and their synergy on the maintenance of the hepatocyte spheroids liver-specific phenotype were assessed in Chapters 2 and 3; it was concluded that the perfusion culture and alginateencapsulation had a positive synergic effect on such hepatic phenotype. The perfusion bioreactor developed in Chapter 3 was used in Chapter 4 for the extended culture of freshly isolated human hepatocytes, as spheroids, from three different donors. These cultures responded to repeated dose drug treatments as expected from mature and differentiated hepatocytes, in up to 4 weeks culture time. In Chapter 5, human embryonic stem cell-derived hepatic progenitors were cultured as spheroids and further differentiated into hepatocyte-like cells; the differential expression of hepatic genes between this spheroid population and a monolayer differentiated hepatocyte-like cell population showed a more efficient differentiation under spheroid culture. The bioengineering improvements of this thesis, as well as the future work, were discussed in Chapter 6. This thesis has led to the establishment and validation of primary cultures of hepatocyte spheroids, in perfusion bioreactors, which can be used for long-term, repeated dose tests in drug development.
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Azuma, Hisaya. "Enrichment of hepatic progenitor cells from adult mouse liver". Kyoto University, 2004. http://hdl.handle.net/2433/147490.
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CATALANO, GIORGIA. "Human liver stem cells and derived products in experimental models of liver ischemia reperfusion injury and of liver isolated normothermic perfusion". Doctoral thesis, Politecnico di Torino, 2018. http://hdl.handle.net/11583/2711047.
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Ischemia reperfusion injury (IRI) is an antigen-independent inflammatory event that affects several
clinical settings, including surgical procedures such as liver resection and liver transplantation. IRI
is still a major concern in the transplantation setting, causing up to 10% of early graft failure and
leading to a higher incidence of acute and chronic rejection. IRI is initiated by Kuppfer cells and
hepatocytes through a massive production of reactive oxygen species (ROS) during the ischemic
phase and, in a major degree, during the post-reperfusion phase. ROS directly damage hepatocytes and endothelial cells and promote the recruiment of neutrophils and T-cells, starting an inflammatory cascade that triggers apoptosis and necrosis.
Human Liver Stem Cells (HLSC) have been identified as a population of pluripotent resident liver
cells able to express markers characteristic of the mesenchymal lineage (CD73, CD90, CD29,
CD44) together with hepatic markers (alpha-fetoprotein, cytokeratin 18, cytokerain 8 and albumin),
suggesting a partial hepatic commitment. HLSC share self-renewal properties with mesenchymal
stem cells and can actively take part to tissue remodeling and liver regeneration. We found that
HLSC are able to localize within the injured tissue and promote liver regeneration in a murine
model of fulminant liver failure and to generate a functional “humanized liver-like tissue” when
injected in rat acellular liver scaffolds. Growing evidence suggests that the biological effects of
stem cells on neighboring cells are mediated by paracrine mechanisms including the release of
extracellular vesicles (EV). EV are an heterogeneous population of cell-secreted vesicles
originating from the endosomal compartment or from direct budding of plasma membrane that are
able to modify the phenotype and function of neighboring cells. The regenerative effects of EV are
well documented and ascribed to a horizontal transfer of proteins, lipids and, above all, specific
subsets of mRNA and miRNA. In a rat model of 70% hepatectomy, animals treated with Human
Liver Stem Cells-derived Extracellular Vesicles (HLSC-EV) revealed a significant reduction of
liver injury and higher regeneration rate of the remnant liver after surgery .
The effect of HLSC-EV was investigated on two different experimental models:
First Project
We set up a short-duration model of ex vivo isolated rat liver Normothermic Machine Perfusion
(NMP) in which oxygen delivery was kept suboptimal through a low hemoglobin
content in the perfusate. In this model, we investigated whether adding HLSC-EV to the circuit
could result in i) their rapid uptake by the liver, and ii) an appreciable reduction of the hypoxic
tissue injury.
Second Project
An in-vivo model of IRI was set up in mice. The aim of this study was to investigate the effects of
systemic administration of HLSC-EV on tissue injury after partial clamping of the hepatic hilum
(70%) .
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Deng, Jie. "Neurogenesis of adult stem cells from the liver and bone marrow". [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0009700.
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Thesis (Ph.D.)--University of Florida, 2005.Typescript. Title from title page of source document. Document formatted into pages; contains 143 pages. Includes Vita. Includes bibliographical references.
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Vyas, Samir Kumar. "Stromelysin-1 and hepatic stellate cells". Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242487.
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Berrie, C. P. "Modulation of calcium signalling in acinar cells and hepatocytes". Thesis, University of Liverpool, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357366.
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Eng, Heather Sui-Fong. "Evaluating the use of cryopreserved hepatocytes for the prediction of in vivo hepatic clearance /". See Full Text at OhioLINK ETD Center (Requires Adobe Acrobat Reader for viewing), 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=toledo1091638312.
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Thesis (M.S.P.)--University of Toledo, 2004.Typescript. "A thesis [submitted] as partial fulfillment of the requirements of the Master of Science degree in Pharmaceutical Sciences." Bibliography: leaves 64-68.
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Moolman, Francis Sean. "Oxygen carriers for a novel bio-artificial liver support system". Pretoria : [s.n.], 2003. http://upetd.up.ac.za/thesis/available/etd-09092004-162043.
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Thesis Ph. D.)(Chemical Engineering)--University of Pretoria, 2003.Title from opening screen (viewed Oct. 06, 2004). Summaries in English and Afrikaans. Includes bibliographical references (leaves 144-151).
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Gaça, Marianna Danuta Aleksandria. "The bi-directional relationship between mast cells and hepatic stellate cells in liver fibrosis". Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323958.
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Golding, Matthew Christian Henry Max. "The behaviour of liver epithelial cells during regeneration and carcinogenesis". Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266028.
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