Relevant bibliographies by topics / Induced-pluripotent Stem Cell-derived Hepatocytes

Academic literature on the topic 'Induced-pluripotent Stem Cell-derived Hepatocytes'

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Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "Induced-pluripotent Stem Cell-derived Hepatocytes"

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Medine, Claire N., Sebastian Greenhough, and David C. Hay. "Role of stem-cell-derived hepatic endoderm in human drug discovery." Biochemical Society Transactions 38, no. 4 (July 26, 2010): 1033–36. http://dx.doi.org/10.1042/bst0381033.

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Accurate prediction of human drug toxicity is a vital part of the drug discovery process. However, the safety evaluation process is hindered by the availability and quality of primary human liver models with which to study drug toxicity. In an attempt to overcome this limitation, research has focused on deriving human hepatocytes from a number of sources, including progenitors from fetal and adult liver, human cell lines derived from liver tumours, immortalized human hepatocytes and pluripotent stem cells. The major hurdles in developing scalable and high-fidelity human hepatocytes from hepatic cell lines and fetal and adult progenitors have been limited organ availability, homogeneous cell purification, short-term cell culture, and the rapid loss of hepatocyte phenotype and function in culture. Therefore it has been necessary to find alternative sources of human hepatocytes which circumvent these issues. The research in our group has focused on generating human hepatic endoderm from the scalable pluripotent stem cell populations, human embryonic stem cells and induced pluripotent stem cells. We have developed efficient and scalable models of human hepatocyte differentiation from these cell populations. Moreover, stem-cell-derived hepatic endoderm displays many of the functional attributes of primary human hepatocytes. Our research is now focused on developing defined culture systems and improving cell culture microenvironments in order to improve our understanding of the mechanisms regulating human liver development. This will in turn facilitate the generation of broad-range functioning hepatic endoderm in vitro. By taking these approaches, we believe that it will be possible to improve the predictive nature of our in vitro models, revolutionizing the manner in which industry measures human drug toxicity and having an impact on drug attrition.
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Hannoun, Zara, Clara Steichen, Noushin Dianat, Anne Weber, and Anne Dubart-Kupperschmitt. "The potential of induced pluripotent stem cell derived hepatocytes." Journal of Hepatology 65, no. 1 (July 2016): 182–99. http://dx.doi.org/10.1016/j.jhep.2016.02.025.

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Shi, Ying, Jiali Deng, Xiaopu Sang, Yihang Wang, Fei He, Xiaoni Chen, Anlong Xu, and Fenfang Wu. "Generation of Hepatocytes and Nonparenchymal Cell Codifferentiation System from Human-Induced Pluripotent Stem Cells." Stem Cells International 2022 (November 22, 2022): 1–18. http://dx.doi.org/10.1155/2022/3222427.

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To date, hepatocytes derived from human-induced pluripotent stem cells (hiPSC) provide a potentially unlimited resource for clinical application and drug development. However, most hiPSC-derived hepatocyte-like cells initiated differentiation from highly purified definitive endoderm, which are insufficient to accurately replicate the complex regulation of signals among multiple cells and tissues during liver organogenesis, thereby displaying an immature phenotypic and short survival time in vitro. Here, we described a protocol to achieve codifferentiation of endoderm-derived hepatocytes and mesoderm-derived nonparenchymal cells by the inclusion of BMP4 into hepatic differentiation medium, which has a beneficial effect on the hepatocyte maturation and lifespan in vitro. Our codifferentiation system suggests the important role of nonparenchymal cells in liver organogenesis. Hopefully, these hepatocytes described here provide a promising approach in the therapy of liver diseases.
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Iwamuro, Masaya, Javed M. Shahid, Kazuhide Yamamoto, and Naoya Kobayashi. "Prospects for Induced Pluripotent Stem Cell-Derived Hepatocytes in Cell Therapy." Cell Medicine 2, no. 1 (April 2011): 1–8. http://dx.doi.org/10.3727/215517911x575975.

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Mann, David A. "Human induced pluripotent stem cell-derived hepatocytes for toxicology testing." Expert Opinion on Drug Metabolism & Toxicology 11, no. 1 (November 11, 2014): 1–5. http://dx.doi.org/10.1517/17425255.2015.981523.

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Pradip, Arvind, Daniella Steel, Susanna Jacobsson, Gustav Holmgren, Magnus Ingelman-Sundberg, Peter Sartipy, Petter Björquist, Inger Johansson, and Josefina Edsbagge. "High Content Analysis of Human Pluripotent Stem Cell Derived Hepatocytes Reveals Drug Induced Steatosis and Phospholipidosis." Stem Cells International 2016 (2016): 1–14. http://dx.doi.org/10.1155/2016/2475631.

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Hepatotoxicity is one of the most cited reasons for withdrawal of approved drugs from the market. The use of nonclinically relevantin vitroandin vivotesting systems contributes to the high attrition rates. Recent advances in differentiating human induced pluripotent stem cells (hiPSCs) into pure cultures of hepatocyte-like cells expressing functional drug metabolizing enzymes open up possibilities for novel, more relevant human cell based toxicity models. The present study aimed to investigate the use of hiPSC derived hepatocytes for conducting mechanistic toxicity testing by image based high content analysis (HCA). The hiPSC derived hepatocytes were exposed to drugs known to cause hepatotoxicity through steatosis and phospholipidosis, measuring several endpoints representing different mechanisms involved in drug induced hepatotoxicity. The hiPSC derived hepatocytes were benchmarked to the HepG2 cell line and generated robust HCA data with low imprecision between plates and batches. The different parameters measured were detected at subcytotoxic concentrations and the order of which the compounds were categorized (as severe, moderate, mild, or nontoxic) based on the degree of injury at isomolar concentration corresponded to previously published data. Taken together, the present study shows how hiPSC derived hepatocytes can be used as a platform for screening drug induced hepatotoxicity by HCA.
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Gieseck III, Richard L., Nicholas R. F. Hannan, Roque Bort, Neil A. Hanley, Rosemary A. L. Drake, Grant W. W. Cameron, Thomas A. Wynn, and Ludovic Vallier. "Maturation of Induced Pluripotent Stem Cell Derived Hepatocytes by 3D-Culture." PLoS ONE 9, no. 1 (January 22, 2014): e86372. http://dx.doi.org/10.1371/journal.pone.0086372.

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Takagi, Chisato, Hiroshi Yagi, Makiko Hieda, Kazuki Tajima, Taizo Hibi, Yuta Abe, Minoru Kitago, Masahiro Shinoda, Osamu Itano, and Yuko Kitagawa. "Mesenchymal Stem Cells Contribute to Hepatic Maturation of Human Induced Pluripotent Stem Cells." European Surgical Research 58, no. 1-2 (September 7, 2016): 27–39. http://dx.doi.org/10.1159/000448516.

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Background: Induced pluripotent stem cells (iPSCs) are human somatic cells that have been reprogrammed to a pluripotent state. Several methods have been used to generate hepatocyte-like cells from iPSCs. However, these hepatic cells have limited clinical application because of their immature function compared to primary hepatocytes. Mesenchymal stem cells (MSCs) have been reported to inhibit apoptosis of hepatic cells and to improve hepatic regeneration in acute liver injury. Therefore, we expected that MSCs had the potential to positively contribute to the maturation of hepatic cells. Here we demonstrate the effect of MSCs on the maturation of hepatoblasts derived from human iPSCs. Methods: MSCs were isolated from human bone marrow and cultured to 70-80% confluence. MSC-conditioned medium (MSC-CM) was collected 48 h after culture in hepatic maturation medium. Human iPSC-derived hepatoblasts were then cultured for 6 days with MSC-CM. Hepatic functions were analyzed and compared to those from cells cultured in general maturation medium. Results: Cells in both groups had a cuboidal morphology typical of hepatocytes. The proportion of Oct4-positive cells was decreased and those of albumin- and alpha-fetoprotein-positive cells were increased in the MSC-CM group. Albumin secretion and urea synthesis as well as cytochrome P450 (CYP) 3A4 activity were enhanced in the MSC-CM group. The gene expressions of some CYP enzymes were upregulated as demonstrated by RT-PCR. Conclusion: Secreted molecules from human MSCs could enhance the hepatic function of human iPSC-derived hepatocyte-like cells. Although more technological innovations are needed, MSC-CM will be useful as a novel efficient strategy for clinically relevant hepatic cell maturation.
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Jeong, Jaemin, Tae Hun Kim, Myounghoi Kim, Yun Kyung Jung, Kyeong Sik Kim, Sehwan Shim, Hyosun Jang, Won Il Jang, Seung Bum Lee, and Dongho Choi. "Elimination of Reprogramming Transgenes Facilitates the Differentiation of Induced Pluripotent Stem Cells into Hepatocyte-like Cells and Hepatic Organoids." Biology 11, no. 4 (March 23, 2022): 493. http://dx.doi.org/10.3390/biology11040493.

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Hepatocytes and hepatic organoids (HOs) derived from human induced pluripotent stem cells (hiPSCs) are promising cell-based therapies for liver diseases. The removal of reprogramming transgenes can affect hiPSC differentiation potential into the three germ layers but not into hepatocytes and hepatic organoids in the late developmental stage. Herein, we generated hiPSCs from normal human fibroblasts using an excisable polycistronic lentiviral vector based on the Cre recombinase-mediated removal of the loxP-flanked reprogramming cassette. Comparing the properties of transgene-carrying and transgene-free hiPSCs with the same genetic background, the pluripotent states of all hiPSCs were quite similar, as indicated by the expression of pluripotent markers, embryonic body formation, and tri-lineage differentiation in vitro. However, after in vitro differentiation into hepatocytes, transgene-free hiPSCs were superior to the transgene-residual hiPSCs. Interestingly, the generation and hepatic differentiation of human hepatic organoids (hHOs) were significantly enhanced by transgene elimination from hiPSCs, as observed by the upregulated fetal liver (CK19, SOX9, and ITGA6) and functional hepatocyte (albumin, ASGR1, HNF4α, CYP1A2, CYP3A4, and AAT) markers upon culture in differentiation media. Thus, the elimination of reprogramming transgenes facilitates hiPSC differentiation into hepatocyte-like cells and hepatic organoids with properties of liver progenitor cells. Our findings thus provide significant insights into the characteristics of iPSC-derived hepatic organoids.
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Inoue, Tomoaki, Norihiko Iwazaki, Tetsuro Araki, and Hiroko Hitotsumachi. "Human-Induced Pluripotent Stem Cell-Derived Hepatocytes and their Culturing Methods to Maintain Liver Functions for Pharmacokinetics and Safety Evaluation of Pharmaceuticals." Current Pharmaceutical Biotechnology 21, no. 9 (June 9, 2020): 773–79. http://dx.doi.org/10.2174/1389201021666200131123524.

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Human hepatocytes are essential cell types for pharmacokinetics and the safety evaluation of pharmaceuticals. However, widely used primary hepatocytes with individual variations in liver function lose those functions rapidly in culture. Hepatic cell lines are convenient to use but have low liver functions. Human-Induced Pluripotent Stem (hiPS) cells can be expanded and potentially differentiated into any cell or tissue, including the liver. HiPS cell-derived Hepatocyte-Like Cells (hiPSHeps) are expected to be extensively used as consistent functional human hepatocytes. Many laboratories are investigating methods of using hiPS cells to differentiate hepatocytes, but the derived cells still have immature liver functions. In this paper, we describe the current uses and limitations of conventional hepatic cells, evaluating the suitability of hiPS-Heps to pharmacokinetics and the safety evaluation of pharmaceuticals, and discuss the potential future use of non-conventional non-monolayer culture methods to derive fully functional hiPS-Heps.
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Dissertations / Theses on the topic "Induced-pluripotent Stem Cell-derived Hepatocytes"

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Szkolnicka, Dagmara Maria. "MicroRNA regulation of drug metabolism in stem cell-derived hepatocytes." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23421.

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The liver is a multi-functional and highly regenerative organ. While resilient, the liver is susceptible to organ damage and failure. In both the acute and chronic settings liver disease has dire consequences for health. A common cause of liver damage is adverse reactions to drugs which can lead to drug induced liver injury (DILI). This creates major problems for patients, clinicians, the pharmaceutical industry and regulatory authorities. In the context of drug overdose or serious adverse reactions, liver failure can be acute and life threatening, and in some cases require orthotopic liver transplantation. While transplantation is highly successful, such an approach has limitations and justifies basic science attempts to develop better human models to study liver injury and to develop scalable intervention strategies. With this in mind, we have studied the importance of microRNAs (miRs) in regulating human drug metabolism in pluripotent stem cell – derived hepatocytes and their potential to reduce liver toxicity in response to toxic levels of paracetamol. miRs are small non-coding RNAs that are approximately 20 - 24 nucleotides long and their major function is to fine tune gene expression of their target genes. Recently, it has been demonstrated that microRNAs play a role in regulating the first phase of drug metabolism however the second phase of drug metabolism, drug conjugation, has not been studied in detail. Drug conjugation is a crucial stage in human drug metabolism, and any alterations in this process can lead to changes in compound pharmacology, including therapeutic dose and clearance from the body. To test the importance of miRs in regulating phase II drug metabolism we opted to study the metabolism of a common used analgesic, paracetamol. When taken in the appropriate amounts paracetamol is modified by sulfotransferases (SULTs) and UDP - glucuronosyltransferases (UGTs) and removed from the body without organ damage. However, when paracetamol is taken above the recommended dose it is metabolised by phase I enzymes to generate a toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which if untreated can lead to massive hepatocyte cell death and liver failure, placing the patient in a life threatening situation. In order to promote non-toxic drug metabolism, in the context of drug overdose, we employed candidate miRs to regulate different parts of the paracetamol metabolism pathway. In summary, we have focused on studying human drug metabolism in the major metabolic cell type of the liver, the hepatocyte. We have identified a novel microRNA (called miR-324-5p) which regulates phase II drug metabolism and reduces cell cytotoxicity. Additionally, a supportive role of anti-microRNA- 324 in response to fulminant plasma collected from paracetamol overdose patients is also observed. The findings of this project are novel, provide proof of concept and exemplify the power of stem cell based models to identify new approaches to treating human liver damage.
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Wills, Lauren Raquel. "Investigating Induced Pluripotent Stem Cells for Tissue Engineering and Hepatotoxicity Applications." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/101006.

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Induced pluripotent stem cells (iPSCs) can be differentiated into multiple cell types in the body while maintaining proliferative capabilities. The generation of human iPSC-derived hepatocytes (iPSC-Heps) has resulted in a new source for hepatic cells. The current available options for human hepatocytes are primary human hepatocytes (PHHs) and cell lines. PHHs isolated from healthy human donors are difficult to obtain, while cell lines exhibit reduced hepatotoxic sensitivity. iPSC-Heps are being investigated as an alternative option as they are derived from a continuous, stable source and are able to maintain their original donor genotype, which opens the door for patient-specific studies. iPSC-Heps show promise for utilization in tissue engineering, hepatotoxicity studies as well as screening for patient-specific therapeutics. Various reports have concluded that iPSC-Heps exhibit reduced hepatocyte function in comparison to PHHs. Prior reports on iPSC-Heps have focused on improving their adult phenotype functions through variations in differentiation protocols or by altering their in vitro culturing environment. This thesis focuses on incorporating hepatic non-parenchymal cells to more closely mimic the tissue and cell architecture found in the liver tissue. We designed and assembled a 3D iPSC-Hep model that integrates liver sinusoidal endothelial cells, with the goal of achieving functional maturity. Hepatotoxicants were administered to our models and various hepatic markers were measured to analyze the toxic response. This work demonstrates the need for the inclusion of hepatic non-parenchymal cells in iPSC-derived liver tissues, specifically for hepatotoxicity applications.
Master of Science
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Chen, Xike. "Integration Capacity of Human Induced Pluripotent Stem Cell-Derived Cartilage." Kyoto University, 2019. http://hdl.handle.net/2433/242390.

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Fatica, Erica Marie. "Investigating Cardiac Metabolism in Barth Syndrome Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes." Cleveland State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=csu1556630870935279.

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Nishimura, Koji. "Transplantation of murine induced pluripotent stem cell-derived neural progenitors into the cochlea." Kyoto University, 2012. http://hdl.handle.net/2433/157416.

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Sachamitr, Supatra. "Exploiting the use of induced pluripotent stem cell derived immune cells for immunotherapy." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:89315b6b-a8cd-4a6f-8c43-3506d8dd1725.

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Immunotherapy traditionally made use of biological agents such as cytokines and monoclonal antibodies. Such first generation therapies lack antigen specificity and fail to induce immunological memory, suggesting that cell therapies may provide the next generation of treatments that are more discerning in their mode of action. Nevertheless, difficulties in obtaining sufficient immunologically-relevant cell types from patients has limited their success. Given that induced pluripotent stem cells (iPSC) may be generated from patients, we have investigated the feasibility of deriving two cell types whose availability is restricted in vivo: regulatory T cells (Tregs) and CD141+ cross-presenting dendritic cells (DCs). We describe the optimization of protocols for differentiation and purification of CD141+ DCs, focussing on their utility as a therapeutic vaccine for HIV-1. We investigate their phenotype, chemotactic capacity, phagocytic ability and propensity to harbour infectious virus. We also assess their immunostimulatory capacity and ability to cross-present exogenous antigen to MHC class I-restricted T cells. Our findings led us to speculate that iPSC-derived DCs (iPDCs) possess fetal phenotype, which is characterised by excessive secretion of IL-10 and failure to secrete IL-12, under all but the most stringent conditions. We hypothesised that constitutive secretion of IL-10 may be responsible for maintaining the fetal phenotype, a hypothesis we tested by developing an appropriate mouse model. iPSCs were derived from WT and IL-10-/- mice and were shown to differentiate into iPDCs which recapitulate the fetal phenotype observed among human cells. However, loss of the endogenous Il-10 gene failed to restore full immunogenicity and IL-12 secretion. Finally, we developed protocols for differentiation of FoxP3+ Tregs from iPSCs, a feat that has not previously been achieved. These findings pave the way for the differentiation of Tregs from iPSCs reprogrammed from antigen-specific pathogenic T cells, thereby creating a source of Tregs with matched specificity for therapeutic intervention.
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Zhang, Jiao, and 张姣. "Regulation of cell proliferation and modulation of differentiation in human induced pluripotent stem cell-derived mesenchumal stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49617503.

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Functional mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (iPSCs) may represent an unlimited cell source with superior therapeutic benefits for tissue regeneration to somatic tissue, such as bone marrow (BM)-derived MSC. In the first part of this project, I investigated whether the differential expression of ion channels in iPSC-MSCs was responsible for their higher proliferation capacity than that of BM-MSCs. The expression of ion channels for K+, Na+, Ca2+ and Cl- currents was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The functional role of these ion channels were then verified by patch clamp experiments to compare the electrophysiological properties of iPSC-MSCs versus BM-MSCs. I detected significant mRNA expression of ion channel genes including KCa1.1, KCa3.1, KCNH1, Kir2.1, SCN9A, CACNA1C and Clcn3 in both human iPSC-MSCs and BM-MSCs; while Kir2.2 and Kir2.3 were only observed in human iPSC-MSCs. Furthermore, I identified five types of currents (BKCa, IKDR, IKir, IKCa and ICl) in iPSC-MSCs, while only four of them (BKCa, IKDR, IKir and IKCa) were observed in BM-MSCs. The rate of cell proliferation was 1.4 fold faster in iPSC-MSCs as compared to BM-MSCs. Interestingly, the proliferation rate of human iPSCMSCs was significantly reduced when inhibiting IKDR with shRNA and hEAG1 channel blockers, 4-AP and astemizole. Though to a lesser extent, the proliferation rate of human BM-MSCs also decreased by IKDR blockage. These results demonstrated that hEAG1 channel plays a crucial role in controlling the proliferation rate of human iPSC-MSCs but to a lesser extent in BM-MSCs. Next, I examined whether forced expression of a transcription factor- myocardin in iPSC-MSC using viral vectors (adenovirus or lentivirus) can further enhance their trans-differentiation to cardiomyocytes and improve their electrophysiological properties for cardiac regeneration. My results on RT-PCR and immunofluorescent staining revealed that myocardin induced the expression of several cardiac and smooth muscle cell markers, including α-MHC, cTnT, GATA4, α-actinin, and cardiac MHC, smooth muscle cell markers MYH11, calponin, and SM α-actin, but not the more mature cardiac markers such as β-MHC and MLC2v in iPSC-MSCs. These findings indicate that forced expression of myocardin in iPSC-MSC resulted in partial trans-differentiation into cardiomyocytes phenotype. Furthermore, I also discovered that myocardin altered the electrophysiological properties of iPSC-MSCs when examined by RT-PCR and patch clamp experiments. Forced expression of myocardin in iPSC-MSC enhanced the expression of Kv4.3, SCN9A and CACNA1C, but reduced that of KCa3.1 and Kir 2.2 in iPSC-MSCs. Moreover, BKCa, IKir, ICl, Ito and INa.TTX were detected in iPSC-MSC with ectopic expression of myocardin; while only BKCa, IKir, ICl, IKDR and IKCa were noted in iPSC-MSC transfected with green florescence protein. Furthermore, as measured by multi-electrode arrays recording plate, the conduction velocity of the neonatal rat ventricular cardiomyocytes cocultured iPSC-MSC monolayer was significantly increased after ectopic expression of myocardin. Taken together, I have demonstrated that hEAG1 channel is important in the regulation of iPSC-MSC proliferation and forced expression of myocardin in iPSC-MSC resulted in their partial transdifferentiation into cardiomyocytes phenotype and improved the electrical conduction during integration with mature cardiomyocytes.
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Medicine
Doctoral
Doctor of Philosophy
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Jambi, Majed. "Differentiation of Human Atrial Myocytes from Endothelial Progenitor Cell-Derived Induced Pluripotent Stem Cells." Thèse, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31158.

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Recent advances in cellular reprogramming have enabled the generation of embryoniclike cells from virtually any cell of the body. These inducible pluripotent stem cells (iPSCs) are capable of indefinite self-renewal while maintaining the ability to differentiate into all cell types. Nowhere will this technology have a greater impact than in the ability to generate disease and patient-specific cell lines. Here we explore the capacity of human iPSCs reprogrammed from peripheral blood endothelial progenitor cells lines to differentiate into atrial myocytes for the study of patient specific atrial physiology. Methods and Results: Late outgrowth endothelial progenitor cells (EPCs) cultured from clinical blood samples provided a robust cell source for genetic reprogramming. Transcriptome analysis hinted that EPCs would be comparatively more amenable to pluripotent reprogramming than the traditional dermal fibroblast. After 6 passages, EPCs were transduced with a doxycycline inducible lentivirus system encoding human transcription factors OCT4, SOX2, KLF4 and Nanog to permit differentiation after removal of doxycycline. The high endogenous expression of key pluripotency transcripts enhanced the ease of iPSC generation as demonstrated by the rapid emergence of typical iPSC colonies. Following removal of doxycycline, genetically reprogrammed EPC-iPSC colonies displayed phenotypic characteristics identical to human embryonic stem cells and expressed high levels of the pluripotent markers SSEA-4, TRA1-60 and TRA1-81. After exposure to conditions known to favor atrial identity, EPC- iPSC differentiating into sheets of beating cardiomyocytes that expressed high levels of several atrial-specific expressed genes (CACNA1H, KCNA5, and MYL4). Conclusions: EPCs provide a stable platform for genetic reprogramming into a pluripotent state using a doxycycline conditional expression system that avoids reexpression of oncogenic/pluripotent factors. Human EPC-derived iPSC can be differentiated into functional cardiomyocytes that express characteristic markers of atrial identity.
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Ruiz-Torres, Sonya Jomara. "Modeling Fanconi Anemia in Squamous Epithelium using Human Induced Pluripotent Stem Cell-Derived Organoids." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1573573103136768.

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Cleary, Elaine Marie. "Effect of C9orf72 hexanucleotide repeat expansions on human induced pluripotent stem cell derived oligodendrocytes." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28816.

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A hexanucleotide repeat expansion in the C9orf72 gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Genetic testing for this pathogenic mutation is challenging due to its GC rich, repetitive nature. I developed PCR based assays to detect the presence of the pathogenic variant, which were used in screening an archival cohort of Scottish ALS patients, and have also been implemented within a diagnostic setting. These PCR assays allow amplification of larger repeat expansions than have previously been reported, and can determine whether a C9orf72 expansion of greater than 100 repeats is present or not. It is not well understood how the repeat expansion leads to disease, but several potential mechanisms have been hypothesised, including reduced expression, RNA toxicity and protein toxicity via dipeptide repeat proteins produced through repeat associated non-AUG translation. Motor neurons are an understandably well studied target in amyotrophic lateral sclerosis, however the role of glia, particularly oligodendrocytes, in the pathogenesis of the disease has recently been highlighted from studies on rodent models and post mortem tissue. To investigate the effect of the C9orf72 repeat expansion on oligodendrocytes, we have applied a differentiation protocol to hiPSCs with the expansion and controls, including an isogenic control which has been generated in the lab. There was no difference in the production of neuronal and glial cell types between these cell lines. I went on to look for evidence of the main proposed pathological mechanisms of C9orf72 repeat expansions: loss of function or gain of function through either RNA or protein toxicity. hiPSC derived oligodendrocytes from both carrier and control showed low expression of C9orf72 mRNA, and there was no difference due to the presence of a repeat expansion. Carrier hiPSC derived oligodendrocytes displayed sense RNA foci, which did not appear to have an effect on cellular morphology. The detection of dipeptide repeat proteins proved challenging, and the results were inconclusive as to their presence in hiPSC derived oligodendrocytes. I went on to show there was no evidence of mislocalisation of TDP-43 in C9orf72 carrier oligodendrocytes. Finally, the study showed similar levels of cell death in basal conditions in carrier and control cells, and no clear difference in the response to endoplasmic reticulum stress. Further research will be required to elucidate the role of oligodendrocytes in C9orf72 related amyotrophic lateral sclerosis.
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Book chapters on the topic "Induced-pluripotent Stem Cell-derived Hepatocytes"

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Liu, Hua, Pooja Chaudhari, Su Mi Choi, and Yoon-Young Jang. "Applications of Human Induced Pluripotent Stem Cell Derived Hepatocytes." In Stem Cells and Cancer Stem Cells,Volume 3, 213–20. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-2415-0_21.

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Ware, Brenton R., and Salman R. Khetani. "Micropatterned Co-Cultures of Induced Pluripotent Stem Cell-Derived Hepatocytes and Stromal Cells for Drug Toxicity Studies." In Methods in Pharmacology and Toxicology, 311–34. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-6661-5_16.

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Poulton, Emma-Jane. "Impedance Measurement in Induced Pluripotent Stem Cell-Derived Cardiomyocytes." In Methods in Molecular Biology, 201–9. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-7172-5_11.

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Sinnecker, Daniel, and Alessandra Moretti. "Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Towards Personalized Therapeutic Strategies?" In Channelopathies in Heart Disease, 421–37. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-77812-9_16.

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Yoshinaga, Daisuke, Yimin Wuriyanghai, and Takeru Makiyama. "Multielectrode Array Assays Using Human-Induced Pluripotent Stem Cell-Derived." In Methods in Molecular Biology, 111–19. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1484-6_12.

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Dash, Biraja C. "Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells for Vascular Regeneration." In Stem Cell Therapy for Vascular Diseases, 199–219. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-56954-9_9.

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Lau, Vivian W., Simon R. Platt, Steven L. Stice, and Franklin D. West. "Induced Pluripotent Stem-Cell-Derived Neural Cell Types in Treatment of Stroke." In Cell Therapy for Brain Injury, 147–72. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-15063-5_10.

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Lin, Lisa, Tiffany Barszczewski, Patrick G. Burgon, and Glen F. Tibbits. "Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform for Modeling Arrhythmias." In Handbook of Stem Cell Therapy, 1–19. Singapore: Springer Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-6016-0_44-1.

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Lin, Lisa, Tiffany Barszczewski, Patrick G. Burgon, and Glen F. Tibbits. "Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform for Modeling Arrhythmias." In Handbook of Stem Cell Therapy, 875–93. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-2655-6_44.

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Biendarra-Tiegs, Sherri M., Frank J. Secreto, and Timothy J. Nelson. "Addressing Variability and Heterogeneity of Induced Pluripotent Stem Cell-Derived Cardiomyocytes." In Advances in Experimental Medicine and Biology, 1–29. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/5584_2019_350.

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Conference papers on the topic "Induced-pluripotent Stem Cell-derived Hepatocytes"

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van der Stegen, Sjoukje J. C., Maria Themeli, Justin Eyquem, Jorge Mansilla-Soto, and Michel Sadelain. "Abstract 2309: T-cell development from T cell-derived induced pluripotent stem cell." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2309.

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Li, Lulu, Rene Schloss, Noshir Langrana, and Martin Yarmush. "Effects of Encapsulation Microenvironment on Embryonic Stem Cell Differentiation." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192587.

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Pluripotent embryonic stem cells represent a promising renewable cell source to generate a variety of differentiated cell types. Although many investigators have described techniques to effectively differentiate stem cells into different mature cell lineages, their practicality is limited by the absence of large scale processing consideration and low yields of differentiated cells. Previously we have established a murine embryonic stem cell alginate-poly-l-lysine microencapsulation differentiation system. The three-dimensional alginate microenvironment maintains cell viability, is conducive to ES cell differentiation to hepatocyte lineage cells, and maintains differentiated cellular function. In the present work, we demonstrate that hepatocyte differentiation is mediated by cell-cell aggregation in the encapsulation microenvironment. Both cell aggregation and hepatocyte functions, such as urea and albumin secretion, as well as increased expression of cytokaratin 18 and cyp4507a, occur concomitantly with surface E-cadherin expression. Furthermore, by incorporating soluble inducers, such as retinoic acid, into the permeable microcapsule system, we demonstrate decreased cell aggregation and enhanced neuronal lineage differentiation with the expression of various neuronal specific markers, including neurofilament, A2B5, O1 and GFAP. Therefore, as a result of capsule parameter and microenvironment manipulation, we are capable of targeting cellular differentiation to both endodermal and ectodermal cell lineages.
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Rodriguez, Marita L., Charles E. Murry, and Nathan J. Sniadecki. "Assessment of Induced Pluripotent Stem Cell-Derived Cardiomyocyte Contractility Using Micropost Arrays." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14640.

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Cardiovascular stem cell therapies have shown increasing promise as a potential therapeutic means for reversing the effects of a myocardial infarction [1]. Out of the currently available sources of human stem cells, human induced pluripotent stem cells (hiPSCs) are very promising in that: the number of cell lines that can be induced to the pluripotent state is extremely vast, they serve as a potential source for patient-specific cardiomyocytes, and their use is non-controversial. However, before they can be used feasibly in a clinical setting, the functional engraftment of these cells into the host tissue must be improved [2]. It is hypothesized that the structural and functional maturity of the stem-cell derived cardiomyocytes prior to implantation, may significantly affect the ability of these cells to engraft with resident heart tissue [3]. One of the most important functional characteristics of a cardiomyocyte is its ability to produce contractile forces. However, assessing the contractile properties of single iPS-CMs is a difficult task. iPS-CMs generally have relatively unorganized cytoskeletons, with stress fibers in multiple directions. This trait renders one or two-point force assays ineffectual in determining total cell forces. Furthermore, iPS-CMs don’t spread well on tissue culture surfaces, which make two-dimensional force measurements almost impossible.
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Ptasinski, V., S. Monkley, M. Tammia, K. Öst, C. Overed-Sayer, P. Hazon, D. E. Wagner, and L. A. Murray. "Modeling idiopathic pulmonary fibrosis using induced pluripotent stem cell-derived alveolar epithelial organoids." In ERS Lung Science Conference 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/23120541.lsc-2021.62.

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Gilpin, Sarah, Tong Wu, Dan Gorman, Liye Zhu, Daniele Evangelista-Leite, Marall Vedaie, Darrell Kotton, and Harald Ott. "Engineering distal pulmonary epithelium from induced pluripotent stem cell (iPSC)-derived alveolar cells." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa587.

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Folkmanaite, Milda, Xin Zhou, Francesca Margara, Manuela Zaccolo, and Blanca Rodriguez. "In Silico Human Induced Pluripotent Stem Cell Derived Cardiomyocyte Electro-Mechanical Modelling and Simulation." In 2021 Computing in Cardiology (CinC). IEEE, 2021. http://dx.doi.org/10.23919/cinc53138.2021.9662938.

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Mizutani, Akifumi, Shuichi Matsuda, Tin Yan, Tatsuyuki Sota, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, and Masaharu Seno. "Abstract 2647:In vitroniche created by cancer stem-like cells derived from mouse induced pluripotent stem cell." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2647.

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Jones, Casey M., Kasim L. Mirza, Bradley J. Blakley, Dusan Pavcnik, and Monica T. Hinds. "A Treatment for Chronic Deep Venous Insufficiency Utilizing Induced Pluripotent Stem Cell Derived Endothelial Cells." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14628.

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Chronic deep venous insufficiency (CDVI) is a disease caused by incompetent venous valves in the deep veins which result in venous reflux and pooling of blood in the lower extremities. Symptoms include edema, skin changes, and ulceration. It is estimated that over six million people in the United States are affected by this disease and symptoms can be recurring, leading to an underestimation of the prevalence. The current treatments of CDVI are management techniques to encourage blood flow and oxygen transport, including compression, elevation, and exercise; strategies to repair or replace the incompetent valves are lacking.
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Victoria, Ptasinski, Susan Monkley, Markus Tammia, Karolina Öst, Catherine Overed-Sayer, Petra Hazo, Darcy E. Wagner, and Lynne A. Murray. "LSC - 2021 - Modeling idiopathic pulmonary fibrosis using induced pluripotent stem cell-derived alveolar epithelial organoids." In ERS International Congress 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/13993003.congress-2021.pa2051.

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Huang, J., C. Villacorta-Martin, and D. N. Kotton. "Single-Cell Analysis of Self-Renewal Mechanisms in Human Induced Pluripotent Stem Cell-Derived Alveolar Epithelial Type 2 Cells." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a6405.

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Reports on the topic "Induced-pluripotent Stem Cell-derived Hepatocytes"

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Donohue, Henry J., Christopher Niyibizi, and Alayna Loiselle. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss. Fort Belvoir, VA: Defense Technical Information Center, September 2013. http://dx.doi.org/10.21236/ada606237.

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Donahue, Henry J. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss. Fort Belvoir, VA: Defense Technical Information Center, July 2012. http://dx.doi.org/10.21236/ada581680.

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Maragakis, Nicholas J., and Hongjun Song. Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS. Fort Belvoir, VA: Defense Technical Information Center, December 2014. http://dx.doi.org/10.21236/ada613757.

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Maragakis, Nicholas J., and Hongjun Song. Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS. Fort Belvoir, VA: Defense Technical Information Center, October 2012. http://dx.doi.org/10.21236/ada568166.

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Maragakis, Nicholas J., and Hongjun Song. Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS. Fort Belvoir, VA: Defense Technical Information Center, October 2011. http://dx.doi.org/10.21236/ada555307.

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