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Letteratura scientifica selezionata sul tema "Induced pluripotent stem cells IPSC"

Autore: Grafiati

Pubblicato: 1 marzo 2025

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Articoli di riviste sul tema "Induced pluripotent stem cells IPSC"

Sarker, Drishty B., Yu Xue, Faiza Mahmud, Jonathan A. Jocelyn e Qing-Xiang Amy Sang. "Interconversion of Cancer Cells and Induced Pluripotent Stem Cells". Cells 13, n. 2 (10 gennaio 2024): 125. http://dx.doi.org/10.3390/cells13020125.

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Cancer cells, especially cancer stem cells (CSCs), share many molecular features with induced pluripotent stem cells (iPSCs) that enable the derivation of induced pluripotent cancer cells by reprogramming malignant cells. Conversely, normal iPSCs can be converted into cancer stem-like cells with the help of tumor microenvironment components and genetic manipulation. These CSC models can be utilized in oncogenic initiation and progression studies, understanding drug resistance, and developing novel therapeutic strategies. This review summarizes the role of pluripotency factors in the stemness, tumorigenicity, and therapeutic resistance of cancer cells. Different methods to obtain iPSC-derived CSC models are described with an emphasis on exposure-based approaches. Culture in cancer cell-conditioned media or cocultures with cancer cells can convert normal iPSCs into cancer stem-like cells, aiding the examination of processes of oncogenesis. We further explored the potential of reprogramming cancer cells into cancer-iPSCs for mechanistic studies and cancer dependencies. The contributions of genetic, epigenetic, and tumor microenvironment factors can be evaluated using these models. Overall, integrating iPSC technology into cancer stem cell research holds significant promise for advancing our knowledge of cancer biology and accelerating the development of innovative and tailored therapeutic interventions.

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Slukvin, Igor. "Induced Pluripotent Stem Cells and Erythrocyte Production". Blood 120, n. 21 (16 novembre 2012): SCI—38—SCI—38. http://dx.doi.org/10.1182/blood.v120.21.sci-38.sci-38.

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Abstract Abstract SCI-38 Induced pluripotent stem cells (iPSCs) are somatic cells that have been turned into embryonic-like stem cells by forced expression of factors critical for establishing pluripotency. Because iPSCs can be differentiated into any type of cell in the human body, including hematopoietic cells, they are seen as a logical alternative source of red blood cells (RBCs) for transfusion. In addition, the unlimited expansion potential of iPSCs makes it easy to adopt iPSC technology for RBC biomanufacturing. iPSCs can be generated from any type of donor, including O/Rh-negative universal donors and donors with very rare blood phenotypes, which makes it possible to generate blood products to accommodate virtually all patient groups. We have developed an approach for generating large quantities of RBCs from iPSCs by inducing them to differentiate into CD34+CD43+ hematopoietic progenitors in coculture with OP9 stromal cells, followed by selective expansion of erythroid cells in serum-free media with erythropoiesis-supporting cytokines. Erythroid cultures produced by this approach consist of leukocyte-free populations of CD235a+ RBCs with robust expansion potential and long (up to 90 days) life spans. In these cultures, up to 1.8×105 RBCs can be generated from a single iPSC. Similar to embryonic stem cells, iPSC-derived RBCs express predominantly embryonic and fetal hemoglobin, with very little adult hemoglobin. It is already feasible to adopt iPSC technologies for producing cGMP-grade RBCs using defined animal-product-free differentiation conditions. However, the induction of the complete switch from embryonic to fetal and adult hemoglobin, as well as the terminal maturation and enucleation of iPSC-derived erythroid cells, remains a significant challenge. We recently identified at least three distinct waves of hematopoietic progenitors with erythroid potential in iPSC differentiation cultures. The characterization of erythroid cells produced from these waves of hematopoiesis may help to define populations with definitive erythroid potential and facilitate the production of erythrocytes from iPSCs. Additional critical steps toward translating iPSC-based RBC technologies to the clinic include the development of bioreactor-based-technology for further scaling-up of cell production, and evaluation of the therapeutic potential and safety of human pluripotent stem cell-derived blood cells in animal models. Overall, the manufacturing of RBCs provides several advantages. It can improve the continuity of the blood supply, minimize/eliminate the risk of infection transmission, reduce the incidence of hemolytic and nonhemolytic transfusion reactions, and provide an opportunity to generate RBCs that fit specific clinical needs by using genetically engineered iPSCs or iPSCs with rare blood groups. Disclosures: Slukvin: CDI: Consultancy, Equity Ownership; Cynata: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

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Zhou, Yang, Miao Li, Kuangyi Zhou, James Brown, Tasha Tsao, Xinjian Cen, Tiffany Husman, Aarushi Bajpai, Zachary Spencer Dunn e Lili Yang. "Engineering-Induced Pluripotent Stem Cells for Cancer Immunotherapy". Cancers 14, n. 9 (1 maggio 2022): 2266. http://dx.doi.org/10.3390/cancers14092266.

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Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an “unlimited supply” for cell therapy because of their unique self-renewal properties and the capacity to be genetically engineered. iPSCs can be differentiated into different immune cells, such as T cells, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma delta T (γδ T), mucosal-associated invariant T (MAIT) cells, and macrophages (Mφs). In this review, we describe iPSC-based allogeneic cell therapy, the different culture methods of generating iPSC-derived immune cells (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-γδT, iPSC-MAIT and iPSC-Mφ), as well as the recent advances in iPSC-T and iPSC-NK cell therapies, particularly in combinations with CAR-engineering. We also discuss the current challenges and the future perspectives in this field towards the foreseeable applications of iPSC-based immune therapy.

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Chang, Chia-Yu, Hsiao-Chien Ting, Ching-Ann Liu, Hong-Lin Su, Tzyy-Wen Chiou, Horng-Jyh Harn e Shinn-Zong Lin. "Induced Pluripotent Stem Cells". Cell Transplantation 27, n. 11 (12 giugno 2018): 1588–602. http://dx.doi.org/10.1177/0963689718775406.

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Many neurodegenerative diseases are progressive, complex diseases without clear mechanisms or effective treatments. To study the mechanisms underlying these diseases and to develop treatment strategies, a reliable in vitro modeling system is critical. Induced pluripotent stem cells (iPSCs) have the ability to self-renew and possess the differentiation potential to become any kind of adult cell; thus, they may serve as a powerful material for disease modeling. Indeed, patient cell-derived iPSCs can differentiate into specific cell lineages that display the appropriate disease phenotypes and vulnerabilities. In this review, we highlight neuronal differentiation methods and the current development of iPSC-based neurodegenerative disease modeling tools for mechanism study and drug screening, with a discussion of the challenges and future inspiration for application.

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Ohnuki, Mari, e Kazutoshi Takahashi. "Present and future challenges of induced pluripotent stem cells". Philosophical Transactions of the Royal Society B: Biological Sciences 370, n. 1680 (19 ottobre 2015): 20140367. http://dx.doi.org/10.1098/rstb.2014.0367.

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Growing old is our destiny. However, the mature differentiated cells making up our body can be rejuvenated to an embryo-like fate called pluripotency which is an ability to differentiate into all cell types by enforced expression of defined transcription factors. The discovery of this induced pluripotent stem cell (iPSC) technology has opened up unprecedented opportunities in regenerative medicine, disease modelling and drug discovery. In this review, we introduce the applications and future perspectives of human iPSCs and we also show how iPSC technology has evolved along the way.

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Yulin, X., L. Lizhen, Z. Lifei, F. Shan, L. Ru, H. Kaimin e He Huang. "Efficient Generation of Induced Pluripotent Stem Cells from Human Bone Marrow Mesenchymal Stem Cells". Folia Biologica 58, n. 6 (2012): 221–30. http://dx.doi.org/10.14712/fb2012058060221.

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Ectopic expression of defined sets of genetic factors can reprogramme somatic cells to induced pluripotent stem cells (iPSCs) that closely resemble embryonic stem cells. However, the low reprogramming efficiency is a significant handicap for mechanistic studies and potential clinical application. In this study, we used human bone marrow-derived mesenchymal stem cells (hBMMSCs) as target cells for reprogramming and investigated efficient iPSC generation from hBMMSCs using the compounds of p53 siRNA, valproic acid (VPA) and vitamin C (Vc) with four transcription factors OCT4, SOX2, KLF4, and c-MYC (compound induction system). The synergetic mechanism of the compounds was studied. Our results showed that the compound induction system could efficiently reprogramme hBMMSCs to iPSCs. hBMMSC-derived iPSC populations expressed pluripotent markers and had multi-potential to differentiate into three germ layer-derived cells. p53 siRNA, VPA and Vc had a synergetic effect on cell reprogramming and the combinatorial use of these substances greatly improved the efficiency of iPSC generation by suppressing the expression of p53, decreasing cell apoptosis, up-regulating the expression of the pluripotent gene OCT4 and modifying the cell cycle. Therefore, our study highlights a straightforward method for improving the speed and efficiency of iPSC generation and provides versatile tools for investigating early developmental processes such as haemopoiesis and relevant diseases. In addition, this study provides a paradigm for the combinatorial use of genetic factors and molecules to improve the efficiency of iPSC generation.

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Choi, Kyung-Dal, Junying Yu, Kimberly Smuga-Otto, Jessica Dias, Giorgia Salvagiotto, Maxim Vodyanik, James Thomson e Igor Slukvin. "Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells". Blood 112, n. 11 (16 novembre 2008): 731. http://dx.doi.org/10.1182/blood.v112.11.731.731.

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Abstract Induced pluripotent stem cells (iPSCs) provide an unprecedented opportunity for modeling of human diseases in vitro as well as for developing novel approaches for regenerative therapy based on immunologically compatible cells. In the present study, we employed an OP9 differentiation system to characterize the hematopoietic differentiation potential of seven human iPSC lines obtained from human fetal, neonatal, and adult fibroblasts through reprogramming with POU5F1, SOX2, NANOG, and LIN28 and compared it with the differentiation potential of five human embryonic stem cell lines (hESC; H1, H7, H9, H13, and H14). Similar to hESCs, all iPSCs in coculture with OP9 generated all types of colony forming cells (CFCs) as well as CD34+ cells that can be separated into distinct subsets based on differential expression of CD43 and CD31. CD34+CD31+CD43− cells obtained from all iPSCs expressed molecules present on endothelial cells and readily formed a monolayer when placed in endothelial conditions, while hematopoietic CFC potential was restricted to CD43+ cells. iPSC-derived CD43+ cells could be separated into three major subsets based on differential expression of CD235a/CD41a and CD45: CD235a+CD41a+/− (erythro-megakaryocytic progenitors), and lin-CD34+CD43+CD45− (multipotent), and lin-CD34+CD43+CD45+ (myeloid-skewed) primitive hematopoietic cells. Both subsets of primitive hematopoietic cells expressed genes associated with myeloid and lymphoid development, although myeloid genes were upregulated in CD45+ cells, which are skewed toward myeloid differentiation. Cytogenetic analysis demonstrated that iPSCs and derived from them CD43+ cells maintained normal karyotype. In addition short tandem repeat analysis of CFCs generated from IMR90-1 cells has been performed to confirm that blood cells are in fact derived from reprogrammed IMR90 cells, and not from contaminating hESCs. While we observed some variations in the efficiency of hematopoietic differentiation between different iPSCs, the pattern of differentiation was very similar in all seven tested iPSC and five hESC lines. Using different cytokine combinations and culture conditions we were able to expand iPSC-derived myeloid progenitors and induce their differentiation toward red blood cells, neutrophils, eosinophils, macrophages, ostoeclasts, dendritic and Langerhans cells. Although several issues remain to be resolved before iPSC-derived blood cells can be administered to humans for therapeutic purposes, patient-specific iPSCs can already be used for characterization of mechanisms of blood diseases and to identify molecules that can correct affected genetic networks.

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Yang, Guang, Hyenjong Hong, April Torres, Kristen Malloy, Gourav Choudhury, Jeffrey Kim e Marcel Daadi. "Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural Stem Cells and Dopaminergic Lineage". International Journal of Molecular Sciences 19, n. 9 (17 settembre 2018): 2788. http://dx.doi.org/10.3390/ijms19092788.

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Humans and nonhuman primates (NHP) are similar in behavior and in physiology, specifically the structure, function, and complexity of the immune system. Thus, NHP models are desirable for pathophysiology and pharmacology/toxicology studies. Furthermore, NHP-derived induced pluripotent stem cells (iPSCs) may enable transformative developmental, translational, or evolutionary studies in a field of inquiry currently hampered by the limited availability of research specimens. NHP-iPSCs may address specific questions that can be studied back and forth between in vitro cellular assays and in vivo experimentations, an investigational process that in most cases cannot be performed on humans because of safety and ethical issues. The use of NHP model systems and cell specific in vitro models is evolving with iPSC-based three-dimensional (3D) cell culture systems and organoids, which may offer reliable in vitro models and reduce the number of animals used in experimental research. IPSCs have the potential to give rise to defined cell types of any organ of the body. However, standards for deriving defined and validated NHP iPSCs are missing. Standards for deriving high-quality iPSC cell lines promote rigorous and replicable scientific research and likewise, validated cell lines reduce variability and discrepancies in results between laboratories. We have derived and validated NHP iPSC lines by confirming their pluripotency and propensity to differentiate into all three germ layers (ectoderm, mesoderm, and endoderm) according to standards and measurable limits for a set of marker genes. The iPSC lines were characterized for their potential to generate neural stem cells and to differentiate into dopaminergic neurons. These iPSC lines are available to the scientific community. NHP-iPSCs fulfill a unique niche in comparative genomics to understand gene regulatory principles underlying emergence of human traits, in infectious disease pathogenesis, in vaccine development, and in immunological barriers in regenerative medicine.

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Dai, Rui, Ricardo Rossello, Chun-chun Chen, Joeran Kessler, Ian Davison, Ute Hochgeschwender e Erich D. Jarvis. "Maintenance and Neuronal Differentiation of Chicken Induced Pluripotent Stem-Like Cells". Stem Cells International 2014 (2014): 1–14. http://dx.doi.org/10.1155/2014/182737.

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Pluripotent stem cells have the potential to become any cell in the adult body, including neurons and glia. Avian stem cells could be used to study questions, like vocal learning, that would be difficult to examine with traditional mouse models. Induced pluripotent stem cells (iPSCs) are differentiated cells that have been reprogrammed to a pluripotent stem cell state, usually using inducing genes or other molecules. We recently succeeded in generating avian iPSC-like cells using mammalian genes, overcoming a limitation in the generation and use of iPSCs in nonmammalian species (Rosselló et al., 2013). However, there were no established optimal cell culture conditions for avian iPSCs to establish long-term cell lines and thus to study neuronal differentiationin vitro. Here we present an efficient method of maintaining chicken iPSC-like cells and for differentiating them into action potential generating neurons.

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Wattanapanitch, Methichit. "Recent Updates on Induced Pluripotent Stem Cells in Hematological Disorders". Stem Cells International 2019 (2 maggio 2019): 1–15. http://dx.doi.org/10.1155/2019/5171032.

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Over the past decade, enormous progress has been made in the field of induced pluripotent stem cells (iPSCs). Patients’ somatic cells such as skin fibroblasts or blood cells can be used to generate disease-specific pluripotent stem cells, which have unlimited proliferation and can differentiate into all cell types of the body. Human iPSCs offer great promises and opportunities for treatments of degenerative diseases and studying disease pathology and drug screening. So far, many iPSC-derived disease models have led to the discovery of novel pathological mechanisms as well as new drugs in the pipeline that have been tested in the iPSC-derived cells for efficacy and potential toxicities. Furthermore, recent advances in genome editing technology in combination with the iPSC technology have provided a versatile platform for studying stem cell biology and regenerative medicine. In this review, an overview of iPSCs, patient-specific iPSCs for disease modeling and drug screening, applications of iPSCs and genome editing technology in hematological disorders, remaining challenges, and future perspectives of iPSCs in hematological diseases will be discussed.

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Più fonti

Tesi sul tema "Induced pluripotent stem cells IPSC"

Sartori, Chiara. "Generation of ovine induced pluripotent stem cells". Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/6491.

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Embryonic stem cells (ESCs) are pluripotent cells derived from the early embryo and are able to differentiate into cells belonging to the three germ layers. They are a valuable tool in research and for clinical use, but their applications are limited by ethical and technical issues. In 2006 a breakthrough report described the generation of induced pluripotent stem cells (iPSCs). IPSCs are ESC-like cells generated from somatic cells by forcing the ectopic expression of specific transcription factors. This circumvents the ethical issues about the use of embryos in research and provides multiple opportunities to understand the mechanisms behind pluripotency. The aim of this project was to generate sheep iPSCs and characterise them. In order to learn the technique I initially repeated the original iPSC methodology: the putative mouse iPSCs I have generated display a morphology typical of ESCs, characterised by a high nuclear to cytoplasmic ratio, and form colonies with neat edges and smooth domes. These cells are positive to Nanog, a marker of pluripotency, and can give rise to cells belonging to the mesodermal and the ectodermal lineages when differentiated in vitro. Since the main aim of the thesis was the derivation of sheep pluripotent cells, once established the protocol in mouse, I then moved to the generation of ovine iPSC colonies. The cells I have generated have a morphology similar to that of mouse ESCs, express markers of pluripotency such as alkaline phosphatase and Nanog and can differentiate in vitro and in vivo into cells belonging to the three germ layers. Additionally, these ovine iPSCs can contribute to live born chimeric lambs, although at low level.

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Ababneh, Nidaa. "Modelling of amyotrophic lateral sclerosis (ALS) using induced pluripotent stem cells (iPSC)". Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:b0e48523-2acc-4c1e-83a5-79696cbaf042.

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The hexanucleotide repeat expansion (HRE) mutation within C9orf72 gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Several hypotheses have been proposed for how the mutation contributes to pathogenicity, including the loss of C9orf72 gene function, RNA-mediate toxicity and the formation of toxic dipeptides by repeat-associated non-ATG (RAN) translation. Patient-specific iPSCs provide a promising tool for the study of the cellular and molecular mechanisms of human diseases in relevant cell types and discovering potential therapies. The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-mediated homology directed repair (HDR) system represents an attractive approach for disease modelling and development of therapeutic strategies. In this thesis, iPSCs derived from ALS/FTD patient carrying the HRE mutation were generated and subsequently gene edited to remove a massive repeat expansion from the patient cells and replace it with the wild-type size of the repeats using HDR and a plasmid donor template. The successful genotypic correction of the mutation resulted in the normalization of the C9orf72 gene promoter methylation level and the gene variants RNA expression level. Removal of the mutation also resulted in abolition of sense and antisense RNA foci formation and reduction of DPRs accumulation. Furthermore, the repeat size correction also rescued the susceptibility of cells to Glutamate excitotoxicity, decreased the apoptotic cell death and stress granules formation under the baseline and stress conditions. This work provides a proof-of-principle that removal of the HRE can rescue ALS disease phenotypes and provides an evidence that HRE mutation is an attractive target for therapeutic strategies and drug screening, to block the underlying disease mechanisms.

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Chung, Julia. "Manipulating Somatic Cells to Remove Barriers in Induced Pluripotent Stem Cell Reprogramming". Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:10772.

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Development leads unidirectionally towards a more restricted cell fate that is usually stable. However, it has been proven that developmental systems are reversible by the success of animal cloning of a differentiated somatic genome through somatic cell nuclear transfer (SCNT). Recently, reprogramming of somatic cells to a pluripotent embryonic stem cell (ESC)-like state by introducing defined transcripton factor has been achieved, resulting in the generation of induced pluripotent stem cells (iPSCs), which resemble ESCs. iPSC reprogramming is of great medical interest, as it has the potential to generate a source of patient-specific cells. However, the dangerous delivery method, low efficiency, and slow kinetics of the reprogramming process have hampered progress with this technology.

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Zambon, Federico. "Studying α-Synuclein pathology using iPSC-derived dopaminergic neurons". Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:2856dcf3-0f38-4a37-9242-8c685d1c2c3a.

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Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in the Substantia Nigra pars compacta in the midbrain and the presence of intracellular aggregates, known as Lewy bodies (LBs), in the surviving neurons. The aetiology of PD is unknown but a causative role for α-Synuclein (SNCA) has been proposed. Although the function of αSyn is not well understood, a number of pathological mechanisms associated with αSyn toxicity have been proposed. In this study, nine induced pluripotent stem cells (iPSCs) lines from healthy individuals and PD patients carrying the A53T SNCA mutation or a triplication of SNCA were differentiated to dopaminergic neurons (iDAn). All iPSC lines differentiated with similar efficiency to iDAn, indicating that they could be used for phenotypic analysis. Quantification of αSyn expression showed increased αSyn intracellular staining and the novel detection of increased αSyn oligomerization in PD iDAn. Analysis of mitochondrial respiration found a decrease in basal respiration, maximal respiration, ATP production and spare capacity in PD iDAn, but not in undifferentiated iPSCs, indicating the cell-type specificity of these defects. Decreased phosphorylation of dynamin-1-like protein at Ser616 (DRP1^Ser616) and increased levels of Peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) in A53T SNCA iDAn suggest a new pathological mechanism linking αSyn to the imbalance in mitochondria homeostasis. Markers of endoplasmic reticulum (ER) stress were found to be up-regulated, along with increased β- Glucocerebrosidase (GBA) activity, perturbation of autophagy and decreased expression of fatty acids binding protein 7 (FAPB7) in PD iDAn. Lastly, lentiviral vectors for RNAi-mediated knockdown of αSyn were developed and these reduced αSyn protein levels in iDAn, resulting in increased expression of FABP7. These results describe a novel functional link between αSyn and FABP7. This work demonstrates that iDAn are a promising and relevant in vitro cell model for studying cellular dysfunctions in PD pathology, and the phenotypic analysis of A53T SNCA and SNCA triplication iDAn enabled the detection of novel pathological mechanisms associated with PD.

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Sendfeld, Franziska. "Modelling Brugada Syndrome using induced pluripotent stem cells". Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/19557.

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Objective: Brugada Syndrome is an autosomal dominant congenital heart disease that is responsible for 20% of sudden deaths of patients with structurally normal hearts. The majority of mutations involve the cardiac sodium channel gene SCN5A and give rise to classical symptoms, which include an abnormal electrocardiogram with ST segment elevation and a predisposition to ventricular fibrillation. To date, the implantation of a cardioverter defibrillator is the only proven effective treatment of the disease. The ability to reprogram dermal fibroblasts to induced pluripotent stem (iPS) cells and to differentiate these into cardiomyocytes with the same genetic background provides a novel approach to studying inherited cardiac channelopathies with advantages over existing model systems. Whilst this technique has enormous potential to model inherited channelopathies, such as Brugada Syndrome, the derived cells have not been fully characterised and compared to foetal and adult cardiomyocytes. Methods: Dermal fibroblasts from a patient with Brugada syndrome (SCN5A; c.1100G > A - pARG367HIS) and an age- and sex-matched control were reprogrammed using episomal vectors. All newly derived iPS cell lines were fully characterised using immunocytochemistry, flow cytometry, real-time quantitative reverse transcription PCR and single nucleotide polymorphism analysis and were compared to established human embryonic stem (hES) cell and in-house derived healthy control iPS cell lines. The same control cell lines were used to compare the efficiencies of several cardiac differentiation media. Spontaneously contracting areas, derived from control as well as patient iPS cell lines, were disaggregated and single cardiomyocytes were compared to foetal and adult cardiomyocytes isolated from primary human tissue using immunocytochemistry, transmission electron microscopy, membrane visualisation, calcium imaging and electrophysiology. Results: Comparison of cardiac differentiation protocols using healthy control hES and iPS cell lines found that despite significant inter-line variability with regard to efficiency of cardiac formation guided differentiation protocols could be used to reliably and efficiently generate beating bodies. Spontaneous contraction was observed in stem cell-derived cardiomyocytes and human foetal cardiomyocytes. Pluripotent stem cell-derived cardiomyocytes stained for markers of the cardiac contractile apparatus such as α-actinin, cardiac troponin I and cardiac troponin T. They also expressed functional voltage-activated sodium channels and exhibited action potential triggered calcium-induced calcium release. Stem cell-derived cardiomyocytes showed organisation of myofibrils, ultrastructure and calcium handling more similar to foetal than adult cardiomyocytes. Brugada Syndrome patient-specific cardiomyocytes were structurally indistinguishable from healthy control iPS cell line-derived cardiomyocytes. Electrophysiological analysis of sodium current density confirmed a ~50% reduction in patient-derived compared to healthy control-derived cardiomyocytes. Conclusion: Although iPS cells give rise to a mixture of immature and more mature cardiomyocytes, they all express typical cardiac proteins and have functional cardiac sodium channels. Results illustrate the ability of patient-specific iPS cell technology to model the abnormal functional phenotype of an inherited channelopathy that is independent of structural abnormalities and that the relative immaturity of iPS cell-derived cardiomyocytes does not prevent their use as an accurate model system for channelopathies affecting the cardiac sodium channel Nav1.5. This iPS cell based model system for classical Brugada Syndrome allows for the first time to study the mutation in its native environment and holds promise for further studies to investigate disease mechanisms of known and unknown mutations and to develop new therapies.

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Brightwell, Sara. "Identifying novel regulators of reprogramming using RNA interference". Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/16156.

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Abstract (sommario):

Since Yamanaka and Takahashi first described the isolation of induced pluripotent stem cells (iPSCs) in 2006, researchers have invested a vast amount of time and resources into trying to understand the process of reprogramming. However, the exact mechanisms underlying the induction of somatic cells to pluripotency is still incompletely understood. With this in mind, a screening approach was undertaken to identify shRNA that enhance the reprogramming process. A retrovirus based system was used to knock down candidate genes during reprogramming of mouse embryonic fibroblasts (MEF) containing doxycycline-inducible reprogramming factors and a Nanog-GFP reporter, which is activated when cells become iPSCs. The initial round of screening with over 150 shRNA vectors successfully identified several shRNAs that enhance reprogramming. One of these shRNA vectors exhibited both faster reprogramming kinetics as determined by activation of the Nanog-GFP reporter 2 to 3 days earlier and increased reprogramming efficiency giving rise to >5 fold more GFP+ colonies when compared with a control. Cell surface marker analysis with flow cytometry demonstrated that changes in CD44 and ICAM1 expression, which occur preceding Nanog-GFP expression, were also accelerated. Validation of this shRNA determined that the enhanced reprogramming phenotype is the result of an unknown off-target effect. Microarray and RNA-sequencing analysis was carried out to identify the off target gene with a view to investigate the functional importance of this knock down and its role in establishing the pluripotency transcriptional network during reprogramming.

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Requena, Osete Jordi. "Advancing induced pluripotent stem cell (iPSC) technology by assessing genetic instability and immune response". Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/457970.

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Induced pluripotent stem cells (iPSC) can be made from adult somatic cells by reprogramming them with Oct4, Sox2, Klf4 and c-Myc. IPSC have given rise to a new technology to study and treat human disease (Takahashi et al., 2007). However, before iPSC clinical application, we need to step back and address two main challenges: (i) Genetic stability of iPSC. (ii) Immune response of iPSC-derived cells. To address these key issues, the overall mission of this PhD thesis is to advance iPSC technology by addressing two objectives. First, is to replace c-Myc with Cyclin D1 in the reprogramming cocktail (Oct4, Sox2, Klf4 and c-Myc or Cyclin D1) and second, to study the immune response of iPSC-derived cells. The quality of the starting iPSC determines the quality of the differentiated cells to be transplanted for clinical applications. In terms of genetic stability, aberrant cell reprogramming leads to genetic and epigenetic modifications that are the most significant barriers to clinical applications of patient iPSC derivatives (Gore et al., 2011). Such aberrations can result from the cellular stress that accompanies reprogramming or from the reprogramming factors themselves (Lee et al., 2012a). IPSC made with c-Myc are neoplastic in mouse models and have a higher tumorigenic potential than embryonic stem cells, prompting a search for new pluripotency factors that can replace the oncogenic factors Klf4 and c-Myc (Huangfu et al., 2008; Miura et al., 2009; Okita et al., 2007). We chose Cyclin D1 to replace c-Myc because of previous observation it can be used to reprogram cells to iPSC (Edel et al., 2010) and because of its DNA repair function (Chalermrujinanant et al., 2016). In this thesis we adopt a synthetic mRNA method to demonstrate that Cyclin D1 and c-Myc made iPSC have equal pluripotency using standard methods of characterisation. Moreover, no significant changes in copy number variation were found between starting skin cells and iPSC highlighting it is the method of choice for generating high quality iPSC. Further in- depth analysis revealed that Cyclin D1 made iPSC have reduced genetic instability assessed by: (i) reduced DNA double strand breaks (DSB), (ii) higher nuclear amount of the homologous recombination key protein Rad51, (iii) reduced multitelomeric signals (MTS) and (iv) reduced teratoma growth kinetics in vivo, compared to c-Myc made iPSC. Moreover, we demonstrate that Cyclin D1 iPSC derived neural stem cells engraft successfully, survive long term and differentiate into mature neuron cell types with high efficiency, with no evidence of pathology in a spinal cord injury rat model. As we move towards the clinic with iPSC-derived cells for cell transplantation, the immunogenic response is thought to be one of the main advantages of iPSC technology for clinical application, because of its perceived lack of immune rejection of autologous cell therapy. We hypothesize that iPSC derived cells are unlikely to provoke an immune response. Here we have performed an analysis of the innate and adaptive immune response of human skin cells (termed F1) reprogramed to iPSC and then compared to iPSC-derived cells (termed F2) using proteomic and methylome arrays. We found little differences between MHCI expression and function; however, we discovered a short isoform of the Toll-like receptor 3 (TLR3), essential for viral dsRNA innate immune recognition, which is predominantly upregulated in all iPSC derived cells analysed and not seen in normal endogenous cells. High levels of the TLR3 isoform is associated with unresponsiveness to viral stimulation measured by lack of IL6 secretion in iPSC derived neural stem cells. We propose a new model that TLR3 short isoform competes with the full length wild type isoform destabilizing the essentially required TLR3 dimerization process. These differences could result in supressed inflammatory effects for transplanted human iPSC-derived cells in response to viral or bacterial insult. Further work to determine the in vivo effects is warranted and calls for screening of iPSC lines for TLR3 isoform expression levels before clinical use. In conclusion, this thesis has advanced iPSC technology by defining a new method that is a significant advance with novel insights that has immediate impact on current methods to generate iPSC for clinical application and more accurate disease modelling.
Les cèl·lules mare pluripotents induïdes (iPSC) es poden derivar de cèl·lules somàtiques adultes mitjançant la reprogramació amb Oct4, Sox2, Klf4 i c-Myc. Les iPSC han donat lloc a una nova tecnologia per estudiar i tractar malalties humanes (Takahashi et al., 2007). No obstant, abans de la aplicació clínica de les iPSC, dos problemes principals han de ser adreçats: (i) Estabilitat genètica de les iPSC. (ii) Resposta immune de les cèl·lules derivades de iPSC. Per adreçar aquests dos qüestions cabdals, la missió principal d’aquest doctorat és avançar la tecnologia de les iPSC adreçant dos objectius. El primer, és la substitució de c-Myc per Ciclina D1 al còctel de reprogramació (Oct4, Sox2, Klf4 and c-Myc o Ciclina D1) i segon, estudiar la resposta immune de les cèl·lules derivades de iPSC. Hem escollit Ciclina D1 per substituir c-Myc atès a observacions prèvies que pot ser emprat per reprogramar (Edel et al., 2010) i donada la seva funció en reparació de l’ADN (Chalermrujinanant et al., 2016). Les iPSC reprogramades amb Ciclina D1 presenten una pluripotència similar a les reprogramades amb c-Myc, l’anàlisi en profunditat mostra però, que les iPSC reprogramades amb Cyclin D1 tenen una reduïda inestabilitat genètica adreçada per: (i) reducció en ruptures de doble cadena de DNA, (ii) major quantitat nuclear de la proteïna clau en la recombinació homòloga Rad51, (iii) reducció en senyals multitelomèriques (MTS) i (iv) reducció en la cinètica de creixement de teratomes in vivo, en comparació amb iPSC reprogramades amb c-Myc. A més a més, demostrem que les cèl·lules mare neuronals derivades d’aquestes iPSC son capaces de implantar-se exitosament, sobreviure a llarg termini i diferenciar a neurones madures sense evidències de patologia en un model de dany medul·lar. També hem realitzat un anàlisi del sistema immune innat i adaptatiu de cèl·lules humanes de la pell (nomenades F1) reprogramades a iPSC i comparades amb cèl·lules derivades de iPSC (nomenades F2). Hem descobert una isoforma curta del Toll-Like Receptor 3 (TLR3), essencial en el reconeixement de RNA de doble cadena d’origen víric, que està predominantment sobreexpresada en totes les cèl·lules derivades de iPSC analitzades i no trobat en cèl·lules endògenes. Nosaltres proposem un nou model per el qual la isoforma curta del TLR3 competeix amb la isoforma llarga wild type desestabilitzant el procés essencial de dimerització del TLR3.

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Sharma, Ruchi. "Generation of equine induced pluripotent stem cells from keratinocytes". Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17956.

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Induced pluripotent stem cells (iPSCs) are generated by reprogramming somatic cells to an embryonic state. Therefore iPSCs represent an extremely valuable tool for modelling disease and organ toxicity, with enormous potential in veterinary medicine. Several equine diseases are currently untreatable and can result in euthanasia on medical grounds. In contrast to humans, in vitro models for cellular research in equine do not exist. Therefore it has been necessary to explore the use of stem cells in constructing cell based equine models. Pluripotent stem cell populations are of great interest in this field given their ability to form the three germ layers found in the developing embryo. While a promising notion, the isolation of equine embryonic stem cells has thus far proved elusive and therefore it has been necessary to explore other pluripotent stem cell populations. A very limited number of induced PSC lines have so far been generated from equine fibroblasts but studies in humans showed that other cell types such as keratinocytes were more amenable to reprogramming and generated iPSCs with much higher efficiency; whether this may be also the case in other species has not been investigated. Moreover, iPSC lines reported so far from domestic species, including the horse, depended on complex culture conditions for growth, including feeder layers and media supplementation with several growth factors. Although a promising alternative to fibroblast for generation of induced pluripotent stem cells there is dearth in literature on equine keratinocyte culture techniques. In this work I am reporting a novel approach to generate equine iPSCs lines from keratinocytes. Skin biopsies were used to derive keratinocyte cultures. The three dimensional culture systems were developed for robust culture of equine keratinocytes. These cells were then transduced with retroviral constructs coding for murine Oct-4, Sox-2, c-Myc and Klf-4 sequences, following the original Yamanaka protocol. Following transduction, tight cell colonies with sharp boundaries staining positive for alkaline phosphatase resembling previously reported human iPSCs were generated. The reprogrammed cells were successfully maintained in feeder free and serum free conditions with LIF supplementation. Immunochemistry and qPCR analyses revealed the equine iPSCs lines expressed pluripotency markers expressed in equine embryonic stages including, OCT4, SOX2, SSEA1, LIN 28, NANOG, REX1 and DNMT3B. Equine iPSCs were able to form embryoid bodies and differentiate into derivatives of the three germ layers in vitro. Equine iPSCs were pluripotent in vivo as demonstrated by the formation of teratoma consisting of tissue derivatives of all three lineages such as bone, cartilage, pulmonary epithelium and mature neurons in SCID mice. Importantly, equine iPSCs should not only have the ability to differentiate in a non-directed manner. Therefore, the ability for efficient and directed cellular differentiation was analysed. Equine iPSCs were successfully induced to differentiate into neurospheres forming extensive neuronal projections and synapses. Equine iPSCs were differentiated to neurons using a novel and robust approach. The neurons expressed FOXG1, TUBB3 at induction before ISL1 up regulation, a potent and specific inducer of motor neurons, during terminal differentiation. The neurons tested could fire multiple action potentials and also induce TTX –sensitive action potentials. The iPSC line that showed in vivo differentiation in bone and cartilage was tested for directed differentiation into bone and results were compared to equine mesenchymal stem cells. This study provides the first demonstration of the potential of iPSCs in equine biomedicine. The ability to derive iPSC cells capable of direct differentiation in vitro opens the way for new and exciting applications in equine regenerative medicine.

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GENOVA, ELENA. "Induced pluripotent stem cells as an innovative model for therapy personalization of inflammatory bowel disease". Doctoral thesis, Università degli Studi di Trieste, 2020. http://hdl.handle.net/11368/2961247.

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Crohn’s disease (CD) is a chronic relapsing inflammatory bowel disease that may affect any part of the gastrointestinal tract but most commonly the ileum and the colon. The inflammation extends through the entire thickness of the bowel wall from the mucosa to the serosa. Thiopurines are drugs commonly used in Crohn’s disease (CD) even if some adverse effects are reported. In particular, we focused on the study thiopurine-induced pancreatitis (TIP), a severe and idiosyncratic adverse reaction that affects around 3-5% of CD patients treated with azathioprine, that leads to therapy interruption and could require ad hoc therapy with significative associated costs. Molecular mechanism of TIP is unknown and no validated biomarker is available to assist clinicians in preventing it. Induced pluripotent stem cells (iPSCs) are stem cells obtained reprogramming somatic cells using specific reprogramming factors. iPSCs maintain the donor genetic heritage and have become a powerful technique to model drug adverse effects in a personalized way. iPSCs can differentiate under adequate stimuli into almost every somatic lineage, representing an innovative model to study mechanisms of adverse drug reactions in individual patients' tissues not easily obtainable from human probands. At IRCCS Burlo Garofolo (Trieste, Italy) 3 pediatric CD patients that developed TIP and 3 after azathioprine treatment and 3 CD controls were enrolled and iPSCs were obtained reprogramming peripheral blood mononuclear cells in collaboration with Prof. Gliliani (Brescia, Italy). CD iPSCs were differentiated in pancreatic exocrine cells using the 4 stage protocol developed by Prof. Sasaki (Shinshu University, Japan). Each differentiation stage presents characteristic genetic expression markers: OCT4 is characteristic of undifferentiated cells (iPSCs), FOXA2 and SOX17 of definitive endoderm (stage I), PDX1 of pancreatic progenitors (stage III) and amylase, in particular its pancreatic isoforms AMY2A and AMY2B of pancreatic exocrine cells (stage IV). Differentiation efficiency was analyzed by PCR-real time and immunofluorescence techniques. The sensitivity to thiopurines of TIP and no-TIP CD patient-specific iPSCs and differentiated cells were investigated by MTT assay exposing cells to azathioprine, mercaptopurine and thioguanine for 72 hours. TIP patients iPSCs and pancreatic progenitors resulted more sensitive to mercaptopurine and thioguanine (mercaptopurine p= 0.0162, thioguanine p= 0.0012; two way ANOVA no-TIP vs TIP patients iPSCs; mercaptopurine p = 0.0174; thioguanine p = 0.0144; two way ANOVA no-TIP vs TIP patients pancreatic progenitors). All patients resulted wild type for TPMT polymorphisms letting us to conclude that the different sensitivity between no-TIP and TIP iPSCs and pancreatic progenitors was not related to TPMT genetic variants but to other mechanisms. Thiopurine effect is strictly correlated to cell proliferation being these drugs cell cycle-specific agents interfering during the S phase. iPSCs resulted extremely sensitive to thiopurines in comparison to differentiated cells and to a panel of immortalized lines including the H6C7 ductal pancreatic line. Analysis of cell cycle showed an higher percentage of cells in the S phase in CD-iPSCs with respect to the H6C7 line but not to definitive endoderm or pancreatic progenitors. The faster proliferation of CD-iPSCs well explains their higher sensitivity to thiopurines with respect to H6C7 however, the lower sensitivity of definitive endoderm and pancreatic progenitors cannot be explained basing on the different proliferation of these cells in comparison to iPSCs. The in vitro model established has proven to be suitable for studying and investigating TIP predisposition in a personalized way in pediatric CD patients and could be further developed to study other drugs causing pancreatitis in other diseases.

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O'Malley, James. "Novel cell surface markers identify routes to iPS cells". Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/8883.

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The generation of induced pluripotent stem cells (iPSCs) presents a challenge to normal developmental processes. The low efficiency and heterogeneity of most methods have hindered understanding of the precise molecular mechanisms promoting, and roadblocks preventing, efficient reprogramming. While several intermediate populations have been described, it has proved difficult to characterize the rare, asynchronous transition from these intermediate stages to iPSCs. The rapid expansion of a minor population of reprogrammed cells can also obscure investigation of relevant processes. Understanding of the biological mechanisms essential for successful iPSC generation requires both accurate capture of cells undergoing the reprogramming process and identification of the associated global gene expression changes. Here we demonstrate that reprogramming follows an orderly sequence of stage transitions marked by changes in cell surface markers CD44 and ICAM1, and a Nanog-GFP reporter. RNA-sequencing (RNA-seq) analysis of these populations demonstrates two waves of pluripotency gene up-regulation, and unexpectedly, transient up-regulation of multiple epidermis-related genes, demonstrating that reprogramming is not simply the reversal of normal developmental processes. This novel high-resolution analysis enables the construction of a detailed reprogramming route map, and this improved understanding of the reprogramming process will lead to novel reprogramming strategies.

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Nagy, Andras, e Kursad Turksen, a cura di. Induced Pluripotent Stem (iPS) Cells. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2119-6.

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Turksen, Kursad, e Andras Nagy, a cura di. Induced Pluripotent Stem (iPS) Cells. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3055-5.

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Yildirim, Sibel. Induced Pluripotent Stem Cells. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-2206-8.

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Sullivan, Patrick J. Induced stem cells. Hauppauge, N.Y: Nova Science, 2011.

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Sullivan, Patrick J. Induced stem cells. Hauppauge, N.Y: Nova Science, 2011.

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Ding, Baojin, e Yu Tang, a cura di. Human Induced Pluripotent Stem Cells. New York, NY: Springer US, 2024. http://dx.doi.org/10.1007/978-1-0716-3999-3.

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Turksen, Kursad, a cura di. Induced Pluripotent Stem Cells and Human Disease. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2585-9.

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Ye, Kaiming, e Sha Jin, a cura di. Human Embryonic and Induced Pluripotent Stem Cells. Totowa, NJ: Humana Press, 2012. http://dx.doi.org/10.1007/978-1-61779-267-0.

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Heine, Vivi M., Stephanie Dooves, Dwayne Holmes e Judith Wagner. Induced Pluripotent Stem Cells in Brain Diseases. Dordrecht: Springer Netherlands, 2012. http://dx.doi.org/10.1007/978-94-007-2816-5.

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Zhao, Xiaoyang. Studies of Pluripotency in Embryonic Stem Cells and Induced Pluripotent Stem Cells. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-8819-9.

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Zhao, Xiaoyang. "Developmental Potential of Mouse iPSC". In Studies of Pluripotency in Embryonic Stem Cells and Induced Pluripotent Stem Cells, 75–89. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-8819-9_5.

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Zhao, Xiaoyang. "Pluripotency of iPSC and the Underlining Mechanism". In Studies of Pluripotency in Embryonic Stem Cells and Induced Pluripotent Stem Cells, 53–74. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-8819-9_4.

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Yildirim, Sibel. "Induced Pluripotent Stem Cells (iPSCs)". In SpringerBriefs in Stem Cells, 11–19. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4614-2206-8_3.

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Zhao, Xiaoyang. "Establishment of Highly Efficient Somatic Cell Reprogramming System to Generate iPSC Lines". In Studies of Pluripotency in Embryonic Stem Cells and Induced Pluripotent Stem Cells, 41–52. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-8819-9_3.

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Kumar, Apurva, Laura Stertz e Antonio L. Teixeira. "Induce Pluripotent Stem Cells (iPSC) Technology in Depression". In Advances in Experimental Medicine and Biology, 85–91. Singapore: Springer Nature Singapore, 2024. http://dx.doi.org/10.1007/978-981-97-4402-2_5.

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Karagiannis, Peter. "Clinical Potential of Induced Pluripotent Stem Cells". In Medical Applications of iPS Cells, 3–12. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3672-0_1.

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Pavlović, Mirjana, e Ksenija Radotić. "Induced Pluripotent Stem Cells (iPSCs) and Nuclear Reprogramming". In Animal and Plant Stem Cells, 71–91. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-47763-3_9.

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Woltjen, Knut. "Precision Genome Editing in Human-Induced Pluripotent Stem Cells". In Medical Applications of iPS Cells, 113–30. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-3672-0_7.

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Easley, Charles A. "Induced Pluripotent Stem Cells (iPSCs) in Developmental Toxicology". In Methods in Molecular Biology, 19–34. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9182-2_3.

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Giorgetti, Alessandra, Nuria Montserrat e Juan Carlos Izpisua Belmonte. "Induced Pluripotent Stem Cells (iPSC) from Cord Blood CD133+ Cells Using Oct4 and Sox2". In Springer Protocols Handbooks, 93–111. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-267-0_9.

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Atti di convegni sul tema "Induced pluripotent stem cells IPSC"

Li, Haoran, Jiahua Shi, Huaming Chen, Bo Du, Simon Maksour, Gabrielle Phillips, Mirella Dottori e Jun Shen. "FDNet: Frequency Domain Denoising Network For Cell Segmentation In Astrocytes Derived From Induced Pluripotent Stem Cells". In 2024 IEEE International Symposium on Biomedical Imaging (ISBI), 1–5. IEEE, 2024. http://dx.doi.org/10.1109/isbi56570.2024.10635607.

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Pitta, Marina Galdino da Rocha, Jordy Silva de Carvalho, Luzilene Pereira de Lima e Ivan da Rocha Pitta. "iPSC therapies applied to rehabilitation in parkinson’s disease". In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.022.

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Background: Parkinson’s disease (PD) is a neurological disorder that affects movement, mainly due to damage and degeneration of the nigrostriatal dopaminergic pathway. The diagnosis is made through a clinical neurological analysis where motor characteristics are considered. There is still no cure, and treatment strategies are focused on symptoms control. Cell replacement therapies emerge as an alternative. Objective: This review focused on current techniques of induced pluripotent stem cells (iPSCs). Methods: The search terms used were: “Parkinson’s Disease”, “Stem cells” and “iPSC”. Open articles written in English, from 2016-21 were selected in the Pubmed database, 10 publications were identified. Results: With the modernization of iPSC, it was possible to reprogram pluripotent human somatic cells and generate dopaminergic neurons and individual-specific glial cells. To understand the molecular basis, cell and animal models of neurons and organelles are currently being employed. Organoids are derived from stem cells in a three-dimensional matrix, such as matrigel or hydrogels derived from animals. The neuronal models are: α-synuclein (SNCA), leucine-rich repeat kinase2 (LRRK2), PARK2, putative kinase1 induced by phosphatase and tensin homolog (PINK1), DJ-1. Both models offer opportunities to investigate pathogenic mechanisms of PD and test compounds on human neurons. Conclusions: Cell replacement therapy is promising and has great capacity for the treatment of neurodegenerative diseases. Studies using iPSC neuron and PD organoid modeling is highly valuable in elucidating relevants neuronal pathways and therapeutic targets, moreover providing important models for testing future therapies.

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Gilpin, Sarah, Tong Wu, Dan Gorman, Liye Zhu, Daniele Evangelista-Leite, Marall Vedaie, Darrell Kotton e 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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Gazdhar, Amiq, Iwona Grad, Mathias Gugger, Anis Feki e Thomas Geiser. "Induced Pluripotent Stem Cells (iPSC) Attenuate Fibrosis In Bleomycin Injured Rat Lungs". In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1961.

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Foisset, Florent, Christine Lehalle, Amel Nasri, Isabelle Vachier, Said Assou, Quentin Muller, Vincent Flacher, Arnaud Bourdin, John De Vos e Nelly Frossard. "Construction of a 3D innervated bronchial epithelium from human induced pluripotent stem cells iPSC". In ERS Lung Science Conference 2022 abstracts. European Respiratory Society, 2022. http://dx.doi.org/10.1183/23120541.lsc-2022.183.

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Ahmed, E., M. Fieldes, L. Yakhou, C. Bourguignon, J. Mianné, S. Assou, A. Petit et al. "Modeling trajectories of severe early-onset COPD using human induced pluripotent stem cells (iPSC)." In ERS Lung Science Conference 2024 abstracts. European Respiratory Society, 2024. http://dx.doi.org/10.1183/23120541.lsc-2024.279.

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Tamò, Luca, Amiq Gazdhar, Anis Feki e Thomas Geiser. "The secretome of induced pluripotent stem cells (iPSC) modulates macrophage phenotype in the fibrotic lung". In Annual Congress 2015. European Respiratory Society, 2015. http://dx.doi.org/10.1183/13993003.congress-2015.pa944.

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Rodriguez, Marita L., Charles E. Murry e 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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Ionescu, Lavinia Iuliana, Arul Vadivel, James Ellis e Bernard Thebaud. "Induced Pluripotent Stem Cells (iPSC) Differentiate Into Alveolar Epithelial Cells In Vitro And Improve Lung Function Following Hyperoxia-Induced Lung Injury". In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6535.

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Dane, D. M., K. Cao, K. H. Kernstine, A. Gazdhar, T. K. Geiser e C. C. Hsia. "Inhalational Delivery of Induced Pluripotent Stem Cell (iPSC) Secretome on Canine Post-Pneumonectomy Compensation". In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3842.

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Rapporti di organizzazioni sul tema "Induced pluripotent stem cells IPSC"

Pailino, Lia, Lihua Lou, Alberto Sesena Rubfiaro, Jin He e Arvind Agarwal. Nanomechanical Properties of Engineered Cardiomyocytes Under Electrical Stimulation. Florida International University, ottobre 2021. http://dx.doi.org/10.25148/mmeurs.009775.

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Engineered cardiomyocytes made of human-induced pluripotent stem cells (iPSC) present phenotypical characteristics similar to human fetal cardiomyocytes. There are different factors that are essential for engineered cardiomyocytes to be functional, one of them being that their mechanical properties must mimic those of adult cardiomyocytes. Techniques, such as electrical stimulation, have been used to improve the extracellular matrix's alignment and organization and improve the intracellular environment. Therefore, electrical stimulation could potentially be used to enhance the mechanical properties of engineered cardiac tissue. The goal of this study is to establish the effects of electrical stimulation on the elastic modulus of engineered cardiac tissue. Nanoindentation tests were performed on engineered cardiomyocyte constructs under seven days of electrical stimulation and engineered cardiomyocyte constructs without electrical stimulation. The tests were conducted using BioSoft™ In-Situ Indenter through displacement control mode with a 50 µm conospherical diamond fluid cell probe. The Hertzian fit model was used to analyze the data and obtain the elastic modulus for each construct. This study demonstrated that electrically stimulated cardiomyocytes (6.98 ± 0.04 kPa) present higher elastic modulus than cardiomyocytes without electrical stimulation (4.96 ± 0.29 kPa) at day 7 of maturation. These results confirm that electrical stimulation improves the maturation of cardiomyocytes. Through this study, an efficient nanoindentation method is demonstrated for engineered cardiomyocyte tissues, capable of capturing the nanomechanical differences between electrically stimulated and non-electrically stimulated cardiomyocytes.

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Ying, Mingyao. Modeling Aggressive Medulloblastoma Using Human-Induced Pluripotent Stem Cells. Fort Belvoir, VA: Defense Technical Information Center, luglio 2015. http://dx.doi.org/10.21236/ada620932.

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Chernoff, Jonathan. Induced Pluripotent Stem Cells as Potential Therapeutic Agents in NF1. Fort Belvoir, VA: Defense Technical Information Center, maggio 2012. http://dx.doi.org/10.21236/ada564162.

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Donohue, Henry J., Christopher Niyibizi e Alayna Loiselle. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss. Fort Belvoir, VA: Defense Technical Information Center, settembre 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, luglio 2012. http://dx.doi.org/10.21236/ada581680.

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Peehl, Donna M. Identification of Epigenetic Changes in Prostate Cancer using Induced Pluripotent Stem Cells. Fort Belvoir, VA: Defense Technical Information Center, aprile 2013. http://dx.doi.org/10.21236/ada580354.

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Peehl, Donna. Identification of Epigenetic Changes in Prostate Cancer Using Induced Pluripotent Stem Cells. Fort Belvoir, VA: Defense Technical Information Center, aprile 2011. http://dx.doi.org/10.21236/ada544181.

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Setaluri, Vijayasaradhi. Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development. Fort Belvoir, VA: Defense Technical Information Center, giugno 2014. http://dx.doi.org/10.21236/ada609443.

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