Journal articles on the topic 'Stem cells – Research – Animal models'
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Soria, Bernat, Francisco J. Bedoya, and Franz Martin. "Gastrointestinal Stem Cells I. Pancreatic stem cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 289, no. 2 (August 2005): G177—G180. http://dx.doi.org/10.1152/ajpgi.00116.2005.
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The transplantation of islets isolated from donor pancreas has renewed the interest in cell therapy for the treatment of diabetes. In addition, the capacity that stem cells have to differentiate into a wide variety of cell types makes their use ideal to generate β-cells for transplantation therapies. Several studies have reported the generation of insulin-secreting cells from embryonic and adult stem cells that normalized blood glucose values when transplanted into diabetic animal models. Finally, although much work remains to be done, there is sufficient evidence to warrant continued efforts on stem cell research to cure diabetes.
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Villano, Jason S., Susan E. Vleck, Stephen A. Felt, Daniel D. Myers, and Patrick A. Lester. "Safety Considerations When Working with Humanized Animals." ILAR Journal 59, no. 2 (December 12, 2018): 150–60. http://dx.doi.org/10.1093/ilar/ily012.
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Abstract Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. With this technology comes the need for the animal research enterprise to understand the inherent and potential risks, such as exposure to bloodborne pathogens, associated with the model development and research applications. Here, we review existing humanized animal models and provide recommendations for their safe use based on regulatory framework and literature. A risk assessment program—from handling the human material to its administration to animals and animal housing—is a necessary initial step in mitigating risks associated with the use of humanized animals in research. Ultimately, establishing institutional policies and guidelines to ensure personnel safety is a legal and ethical responsibility of the research institution as part of the occupational health and safety program and overall animal care and use program.
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Kim, Yoon-Young, Jin-Soo Kim, Jeong-Hwan Che, Seung-Yup Ku, Byeong-Cheol Kang, and Jun-Won Yun. "Comparison of Genetically Engineered Immunodeficient Animal Models for Nonclinical Testing of Stem Cell Therapies." Pharmaceutics 13, no. 2 (January 20, 2021): 130. http://dx.doi.org/10.3390/pharmaceutics13020130.
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For the recovery or replacement of dysfunctional cells and tissue—the goal of stem cell research—successful engraftment of transplanted cells and tissues are essential events. The event is largely dependent on the immune rejection of the recipient; therefore, the immunogenic evaluation of candidate cells or tissues in immunodeficient animals is important. Understanding the immunodeficient system can provide insights into the generation and use of immunodeficient animal models, presenting a unique system to explore the capabilities of the innate immune system. In this review, we summarize various immunodeficient animal model systems with different target genes as valuable tools for biomedical research. There have been numerous immunodeficient models developed by different gene defects, resulting in many different features in phenotype. More important, mice, rats, and other large animals exhibit very different immunological and physiological features in tissue and organs, including genetic background and a representation of human disease conditions. Therefore, the findings from this review may guide researchers to select the most appropriate immunodeficient strain, target gene, and animal species based on the research type, mutant gene effects, and similarity to human immunological features for stem cell research.
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Kordiyak, Olena J. "Periodontal Destruction and Regeneration in Experimental Models: Combined Research Approaches." Ukraïnsʹkij žurnal medicini, bìologìï ta sportu 5, no. 5 (October 24, 2020): 28–34. http://dx.doi.org/10.26693/jmbs05.05.028.
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Chronic periodontitis is a common dental disease, resulting in destruction of gingival tissue, periodontal ligament, cementum, alveolar bone and, consequently- teeth loss in the adult population. Experimental animal models have enabled the study of periodontal disease pathogenesis and are used to test new therapeutic approaches for treating the disease The purpose of this review study was to draw the evidence from animal models, required for future assessment of destructional and regenerative processes in periodontal tissues. Material and methods: a rat experimental periodontitis models of ligature, streptozotocin, and immune complexes induced periodontitis, periodontal defect, altered functional loading, stress exposures and surgically created chronic acid reflux esophagitis models. Histomorphomorphological/-metrical, immunohisto (-cyto)chemical and histopathological analysis, micro-computed tomography, scanning and transmission electron microscopy, polarizing light and confocal microscopy, spectrophotometry, radiographic and biomechanical analysis, descriptive histology and computer-assisted image analysis. Results and discussion. Scaling and root planing may not always be effective in preventing periodontal disease progression, and, moreover, with currently available therapies, full regeneration of lost periodontal tissues after periodontitis cannot be achieved. However, in 70.5% of the results of experimental studies reported, irrespective of the defect type and animal model used, beneficial outcome for periodontal regeneration after periodontal ligament stem cell implantation, including new bone, new cementum and new connective tissue formation, was recorded. Therefore, platelet-rich fibrin combined with rat periodontal ligament stem cells provides a useful instrument for periodontal tissue engineering. Conclusion. There is sufficient evidence from preclinical animal studies suggesting that periodontal tissue engineering would provide a valuable tool for periodontal regeneration. Further elaboration of the developed in preclinical studies experimental techniques should justify progress to clinical studies and subsequent medical application
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Norgren, Robert B. "Genetic modification of somatic cells for producing animal models and for cellular transplantation." Reproduction, Fertility and Development 18, no. 8 (2006): 811. http://dx.doi.org/10.1071/rd06074.
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Great progress has been made in two technologies related to biomedical research: (1) manipulating the genomes of cells; and (2) inducing stem cells in culture to differentiate into potentially useful cell types. These technologies can be used to create animal models of human disease and to provide cells for transplantation to ameliorate human disease. Both embryonic stem cells and adult stem cells have been studied for these purposes. Genetically modified somatic cells provide another source of cells for creating animal models and for cellular transplantation.
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Struillou, Xavier, Hervé Boutigny, Assem Soueidan, and Pierre Layrolle. "Experimental Animal Models in Periodontology: A Review." Open Dentistry Journal 4, no. 1 (April 29, 2010): 37–47. http://dx.doi.org/10.2174/1874210601004010037.
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In periodontal research, animal studies are complementary to in vitro experiments prior to testing new treatments. Animal models should make possible the validation of hypotheses and prove the safety and efficacy of new regenerating approaches using biomaterials, growth factors or stem cells. A review of the literature was carried out by using electronic databases (PubMed, ISI Web of Science). Numerous animal models in different species such as rats, hamsters, rabbits, ferrets, canines and primates have been used for modeling human periodontal diseases and treatments. However, both the anatomy and physiopathology of animals are different from those of humans, making difficult the evaluation of new therapies. Experimental models have been developed in order to reproduce major periodontal diseases (gingivitis, periodontitis), their pathogenesis and to investigate new surgical techniques. The aim of this review is to define the most pertinent animal models for periodontal research depending on the hypothesis and expected results.
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Markoski, Melissa Medeiros. "Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice." Scientifica 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/4516920.
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Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals.
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Čamernik, Klemen, Ariana Barlič, Matej Drobnič, Janja Marc, Matjaž Jeras, and Janja Zupan. "Mesenchymal Stem Cells in the Musculoskeletal System: From Animal Models to Human Tissue Regeneration?" Stem Cell Reviews and Reports 14, no. 3 (March 20, 2018): 346–69. http://dx.doi.org/10.1007/s12015-018-9800-6.
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Gergi, Mansour, Sudarshana Sengupta, Prakash Sampath, and Sadhak Sengupta. "EXTH-44. TARGETING GLIOMA STEM CELLS WITH CAR-T IMMUNOTHERAPY IN XENOGRAFT ANIMAL MODELS." Neuro-Oncology 20, suppl_6 (November 2018): vi94. http://dx.doi.org/10.1093/neuonc/noy148.392.
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Kim, Sunil, Su-Jung Shin, Yunjung Song, and Euiseong Kim. "In VivoExperiments with Dental Pulp Stem Cells for Pulp-Dentin Complex Regeneration." Mediators of Inflammation 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/409347.
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In recent years, many studies have examined the pulp-dentin complex regeneration with DPSCs. While it is important to perform research on cells, scaffolds, and growth factors, it is also critical to develop animal models for preclinical trials. The development of a reproducible animal model of transplantation is essential for obtaining precise and accurate datain vivo.The efficacy of pulp regeneration should be assessed qualitatively and quantitatively using animal models. This review article sought to introducein vivoexperiments that have evaluated the potential of dental pulp stem cells for pulp-dentin complex regeneration. According to a review of various researches about DPSCs, the majority of studies have used subcutaneous mouse and dog teeth for animal models. There is no way to know which animal model will reproduce the clinical environment. If an animal model is developed which is easier to use and is useful in more situations than the currently popular models, it will be a substantial aid to studies examining pulp-dentin complex regeneration.
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Wu, Christina C. N., Daniel Jacob Goff, Wenxue Ma, Heather Leu, Thomas A. Lane, and Catriona H. M. Jamieson. "Multiple Myeloma Cancer Stem Cell Animal Model." Blood 114, no. 22 (November 20, 2009): 1848. http://dx.doi.org/10.1182/blood.v114.22.1848.1848.
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Abstract Abstract 1848 Poster Board I-874 Multiple myeloma (MM) is the second most common hematologic malignancy and characterized by clonal proliferation of CD138+ bone marrow plasma cells. Despite various treatment options few patients with MM have been cured. Furthermore, high relapse rates and recent evidence from xenogeneic transplantation models and primary MM marrow samples indicate that a rare population of cells or MM cancer stem cells (MM CSCs) within the marrow regenerates itself and may be responsible for drug resistance. These MM CSCs are phenotypically similar to memory B cells (CD138- CD34-CD19+) but differ in that they have the capacity to regenerate themselves or self-renewal. However, most of the reports on MM CSC animal models are established in NOD/SCID mice that require a larger number (1 – 10 × 106) of bead sorted cells for each animal. In addition, the latency of MM induction (4 – 6 months) in NOD/SCID mouse models and lack of in vivo tracking of the malignant clone preclude robust pre-clinical testing of novel therapeutic strategies that target MM CSC. Mononuclear cells were isolated from autologous mobilized peripheral blood of at least four primary MM patients after Ficoll gradient centrifugation followed by immunomagnetic bead depletion of CD34+ and CD138+ cells and/or further sorted using a FACSAria. The CD138-CD34- population was transduced with lentiviral luciferase GFP (GLF) and transplanted (10,000 to 106 cells per mouse) intrahepatically into neonatal RAG2-/- gamma chain-/- (RAG2-/-gc-/-) mice. Engraftment was compared to mice transplanted with either CD34+ or CD138+ cells. Mice were imaged with an in vivo imaging system (IVIS) to detect bioluminescent engraftment. Results showed that a relatively rare CD138- CD27+ population, resembling memory B cells (∼1.2%), persists in MM autografts and can engraft immunocompromised mice more rapidly and effectively than the CD138+ (Lin+) population of mature plasma cells. This data supports the persistence of CSCs despite high dose chemotherapy further underscoring the need for CSC targeted therapy. Bioluminescence was detected in live mice transplanted with as little as 60,000 cells of CD138- CD34- population and as soon as 4 weeks after transplantation. FACS analysis of these mice demonstrated successful engraftment with the presence of CD45+ and CD138+ population in bone marrow, spleen and liver and bioluminescence was also detected in the secondary transplantation of cells from MMCSC primary engraftment demonstrating the self-renewal capacity of this rare CD138- CD27+ population. Our results suggest that by utilizing a lentiviral GFP-luciferase system in a highly immunocompromised mouse strain fewer cells will be required to monitor MM engraftment and perhaps hasten disease development. Further studies to confirm the expression of selected IgG genes from myeloma cells and to characterize the self-renewal capacity with genes involved in developmental signaling such as sonic hedgehog and wnt pathways are underway. Disclosures: Goff: Coronado Biosciences: Research Funding.
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Tutaev, K. Yu, A. V. Strygin, M. V. Bukatin, B. E. Tolkachev, E. I. Morkovin, N. A. Kolobrodova, A. O. Strygina, et al. "STОСHIOMETRIC MODELS OF ANIMAL CELL METABOLISM: CONCEPT AND APPLICATION IN BIOMEDICAL RESEARCH." Crimea Journal of Experimental and Clinical Medicine 10, no. 2 (2020): 86–94. http://dx.doi.org/10.37279/2224-6444-2020-10-2-86-94.
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The ability to obtain large amounts of heterogeneous data on the components of an animal cell using high-perfor- mance molecular biological technologies necessitates the development of computer data processing methods. One of these methods is the representation of an animal cell as a single biological system through a stoichiometric model of the metabolic network of the cell. The process of cell metabolism over time is considered in such a model as a series of sequential quasistatic states. The model validation procedure includes a number of successive stages: analysis of the metabolic network; confirmation of the conclusions of model analysis by experimental data on a living cell; tuning of model parameters aimed at more accurate imitation of cell metabolism. The model is represented by a directed graph and a mathematical matrix, which display the simultaneous state of stoichiometric equations of enzymatic reactions forming the metabolic network of the cell. When determining the functional state of the metabolic system of a cell, matrix calculations are used; the tasks of optimizing the metabolic functions of a cell are solved by linear program- ming methods and graph theory. An example of the practical application of human cell metabolism models are Recon models. They found practical application in research when determining biomarkers of the action of biologically active substances, studying birth defects in metabolism, identifying side effects of a drug action, determining targets for expo- sure to biologically active substances, and studying cancer cell metabolism. Today, metabolic models of various cells have been created for use in various fields of biomedical research: hepatocytes, cardiomyocytes, astrocytes, kidney cells, adipocytes, red blood cells, blood mononuclear cells, mesenchymal stem cells, platelets, myocytes, sperm cells, enterocytes, endothelial cells, cancer cells, brain neurons.
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Wan, Wenbin, Lan Cao, Bill Kalionis, Shijin Xia, and Xiantao Tai. "Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases." Stem Cells International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/382530.
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Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are permeating many sectors of disease research. Patient sample-derived iPSCs can be used to construct patient-specific disease models to elucidate the pathogenic mechanisms of disease development and to test new therapeutic strategies. Accordingly, the present review will focus on recent progress in iPSC research in the modeling of neurodegenerative disorders and in the development of novel therapeutic options.
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Stephenson, Makeda, Daniel H. Reich, and Kenneth R. Boheler. "Induced pluripotent stem cell-derived vascular smooth muscle cells." Vascular Biology 2, no. 1 (January 9, 2020): R1—R15. http://dx.doi.org/10.1530/vb-19-0028.
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The reproducible generation of human-induced pluripotent stem cell (hiPSC)-derived vascular smooth muscle cells (vSMCs) in vitro has been critical to overcoming many limitations of animal and primary cell models of vascular biology and disease. Since this initial advance, research in the field has turned toward recapitulating the naturally occurring subtype specificity found in vSMCs throughout the body, and honing functional models of vascular disease. In this review, we summarize vSMC derivation approaches, including current phenotype and developmental origin-specific methods, and applications of vSMCs in functional disease models and engineered tissues. Further, we discuss the challenges of heterogeneity in hiPSC-derived tissues and propose approaches to identify and isolate vSMC subtype populations.
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Albert, Katrina, Jonna Niskanen, Sara Kälvälä, and Šárka Lehtonen. "Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia." International Journal of Molecular Sciences 22, no. 9 (April 21, 2021): 4334. http://dx.doi.org/10.3390/ijms22094334.
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Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.
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Mimeault, Murielle, and Surinder K. Batra. "Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells." Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1816, no. 1 (August 2011): 25–37. http://dx.doi.org/10.1016/j.bbcan.2011.03.001.
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McDonough, Ashley, and Verónica Martínez-Cerdeño. "Endogenous Proliferation after Spinal Cord Injury in Animal Models." Stem Cells International 2012 (2012): 1–16. http://dx.doi.org/10.1155/2012/387513.
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Spinal cord injury (SCI) results in motor and sensory deficits, the severity of which depends on the level and extent of the injury. Animal models for SCI research include transection, contusion, and compression mouse models. In this paper we will discuss the endogenous stem cell response to SCI in animal models. All SCI animal models experience a similar peak of cell proliferation three days after injury; however, each specific type of injury promotes a specific and distinct stem cell response. For example, the transection model results in a strong and localized initial increase of proliferation, while in contusion and compression models, the initial level of proliferation is lower but encompasses the entire rostrocaudal extent of the spinal cord. All injury types result in an increased ependymal proliferation, but only in contusion and compression models is there a significant level of proliferation in the lateral regions of the spinal cord. Finally, the fate of newly generated cells varies from a mainly oligodendrocyte fate in contusion and compression to a mostly astrocyte fate in the transection model. Here we will discuss the potential of endogenous stem/progenitor cell manipulation as a therapeutic tool to treat SCI.
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Robbins, J. P., and J. Price. "Human induced pluripotent stem cells as a research tool in Alzheimer's disease." Psychological Medicine 47, no. 15 (August 14, 2017): 2587–92. http://dx.doi.org/10.1017/s0033291717002124.
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Human-induced pluripotent stem cells (iPSCs) offer a novel, timely approach for investigating the aetiology of neuropsychiatric disorders. Although we are starting to gain more insight into the specific mechanisms that cause Alzheimer's disease and other forms of dementia, this has not resulted in therapies to slow the pathological processes. Animal models have been paramount in studying the neurobiological processes underlying psychiatric disorders. Nonetheless, these human conditions cannot be entirely recapitulated in rodents. Human cell models derived from patients’ cells now offer new hope for improving our understanding of the early molecular stages of these diseases, through to validating therapeutics. The impact of dementia is increasing, and a new model to investigate the early stages of this disease is heralded as an essential, new platform for translational research. In this paper, we review current literature using iPSCs to study Alzheimer's disease, describe drug discovery efforts using this platform, and discuss the future potential for this technology in psychiatry research.
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Bryja, Artur, Marta Dyszkiewicz-Konwińska, Joanna Budna, Wiesława Kranc, Adrian Chachuła, Sylwia Ciesiółka, Ewa Sumelka, et al. "Carcinogenesis in mammalian oral mucosa from the perspective of biomedical research." Medycyna Weterynaryjna 73, no. 2 (2017): 82–87. http://dx.doi.org/10.21521/mw.5641.
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Neoplastic diseases are a challenge to modern medicine. The understanding of histological, molecular and genetic transformation leading to cancer is essential in establishing methods for earlier diagnosis and better treatment of oral cavity cancer, not only in humans but also in animals – in particular, in dogs and cats, which develop oral cancer spontaneously. There are several methods of cancer modeling that expand research capabilities. The following overview discusses different methods of inducing carcinogenesis in animals and presents animal models used in the study of carcinogenesis. Publications reviewed in the paper discuss markers used in the diagnosis of oral cancer and describe the concept of cancer stem cells.
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Underbayev, Chingiz, Siddha Kasar, Yao Yuan, and Elizabeth Raveche. "MicroRNAs and Induced Pluripotent Stem Cells for Human Disease Mouse Modeling." Journal of Biomedicine and Biotechnology 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/758169.
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Human disease animal models are absolutely invaluable tools for our understanding of mechanisms involved in both physiological and pathological processes. By studying various genetic abnormalities in these organisms we can get a better insight into potential candidate genes responsible for human disease development. To this point a mouse represents one of the most used and convenient species for human disease modeling. Hundreds if not thousands of inbred, congenic, and transgenic mouse models have been created and are now extensively utilized in the research labs worldwide. Importantly, pluripotent stem cells play a significant role in developing new genetically engineered mice with the desired human disease-like phenotype. Induced pluripotent stem (iPS) cells which represent reprogramming of somatic cells into pluripotent stem cells represent a significant advancement in research armament. The novel application of microRNA manipulation both in the generation of iPS cells and subsequent lineage-directed differentiation is discussed. Potential applications of induced pluripotent stem cell—a relatively new type of pluripotent stem cells—for human disease modeling by employing human iPS cells derived from normal and diseased somatic cells and iPS cells derived from mouse models of human disease may lead to uncovering of disease mechanisms and novel therapies.
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Bonaventura, Gabriele, Rosario Iemmolo, Giuseppe Antonino Attaguile, Valentina La Cognata, Brigida Sabrina Pistone, Giuseppe Raudino, Velia D’Agata, Giuseppina Cantarella, Maria Luisa Barcellona, and Sebastiano Cavallaro. "iPSCs: A Preclinical Drug Research Tool for Neurological Disorders." International Journal of Molecular Sciences 22, no. 9 (April 27, 2021): 4596. http://dx.doi.org/10.3390/ijms22094596.
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The development and commercialization of new drugs is an articulated, lengthy, and very expensive process that proceeds through several steps, starting from target identification, screening new leading compounds for testing in preclinical studies, and subsequently in clinical trials to reach the final approval for therapeutic use. Preclinical studies are usually performed using both cell cultures and animal models, although they do not completely resume the complexity of human diseases, in particular neurodegenerative conditions. To this regard, stem cells represent a powerful tool in all steps of drug discovery. The recent advancement in induced Pluripotent Stem Cells (iPSCs) technology has opened the possibility to obtain patient-specific disease models for drug screening and development. Here, we report the use of iPSCs as a disease model for drug development in the contest of neurological disorders, including Alzheimer’s (AD) and Parkinson’s disease (PD), Amyotrophic lateral Sclerosis (ALS), and Fragile X syndrome (FRAX).
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Zuk, Patricia. "Adipose-Derived Stem Cells in Tissue Regeneration: A Review." ISRN Stem Cells 2013 (February 14, 2013): 1–35. http://dx.doi.org/10.1155/2013/713959.
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In 2001, researchers at the University of California, Los Angeles, described the isolation of a new population of adult stem cells from liposuctioned adipose tissue. These stem cells, now known as adipose-derived stem cells or ADSCs, have gone on to become one of the most popular adult stem cells populations in the fields of stem cell research and regenerative medicine. As of today, thousands of research and clinical articles have been published using ASCs, describing their possible pluripotency in vitro, their uses in regenerative animal models, and their application to the clinic. This paper outlines the progress made in the ASC field since their initial description in 2001, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo, their use in mediating inflammation and vascularization during tissue regeneration, and their potential for reprogramming into induced pluripotent cells.
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Lin, Tai-Chi, Magdalene J. Seiler, Danhong Zhu, Paulo Falabella, David R. Hinton, Dennis O. Clegg, Mark S. Humayun, and Biju B. Thomas. "Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models." Stem Cells International 2017 (2017): 1–19. http://dx.doi.org/10.1155/2017/9428176.
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Dysfunction and death of retinal pigment epithelium (RPE) and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula). Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors) into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities.In vivoexperiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.
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Saha, Sarama, Partha Roy, Cynthia Corbitt, and Sham S. Kakar. "Application of Stem Cell Therapy for Infertility." Cells 10, no. 7 (June 28, 2021): 1613. http://dx.doi.org/10.3390/cells10071613.
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Infertility creates an immense impact on the psychosocial wellbeing of affected couples, leading to poor quality of life. Infertility is now considered to be a global health issue affecting approximately 15% of couples worldwide. It may arise from factors related to the male (30%), including varicocele, undescended testes, testicular cancer, and azoospermia; the female (30%), including premature ovarian failure and uterine disorders; or both partners (30%). With the recent advancement in assisted reproduction technology (ART), many affected couples (80%) could find a solution. However, a substantial number of couples cannot conceive even after ART. Stem cells are now increasingly being investigated as promising alternative therapeutics in translational research of regenerative medicine. Tremendous headway has been made to understand the biology and function of stem cells. Considering the minimum ethical concern and easily available abundant resources, extensive research is being conducted on induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSC) for their potential application in reproductive medicine, especially in cases of infertility resulting from azoospermia and premature ovarian insufficiency. However, most of these investigations have been carried out in animal models. Evolutionary divergence observed in pluripotency among animals and humans requires caution when extrapolating the data obtained from murine models to safely apply them to clinical applications in humans. Hence, more clinical trials based on larger populations need to be carried out to investigate the relevance of stem cell therapy, including its safety and efficacy, in translational infertility medicine.
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Maeshima, Akito, Masao Nakasatomi, and Yoshihisa Nojima. "Regenerative Medicine for the Kidney: Renotropic Factors, Renal Stem/Progenitor Cells, and Stem Cell Therapy." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/595493.
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The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.
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Yang, Guang, Hyenjong Hong, April Torres, Kristen Malloy, Gourav Choudhury, Jeffrey Kim, and Marcel Daadi. "Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural Stem Cells and Dopaminergic Lineage." International Journal of Molecular Sciences 19, no. 9 (September 17, 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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Hollister, S. J., M. B. Wheeler, S. E. Feinberg, and W. L. Murphy. "THE IMPORTANCE OF LARGE ANIMAL MODELS FOR TRANSLATIONAL RESEARCH IN BONE TISSUE ENGINEERING." Reproduction, Fertility and Development 24, no. 1 (2012): 287. http://dx.doi.org/10.1071/rdv24n1ab249.
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The translation of bone tissue engineering (BTE) research to clinical use has been absymal1. Outside of bone void filler biomaterials, only Bone Morphogenetic Protein 2 (BMP2) has made significant inroads to clinical practice, and even BMP2 use has been associated with significant complications including death, dysphagia, and ectopic bone formation. The dearth of BTE products can be attributed to two main causes: (1) the need to develop BTE systems, that successfully integrate scaffolds, growth factors like BMP2 and cells and (2) the need to adapt and implement such systems for a wide variety of clinical indications in CranioMaxilloFacial (CMF), Spine and Orthopedic Surgery. Of course, to fully develop BTE systems (Issue 1) and adapt them to realistic clinical indications, we must be able to test such systems in bone defects that are as close to the human situation as possible. Thus, the use of domestic large animals for bone tissue engineering is critical, as these animals provide challenges in both defect volume and functional loading that can mimic the human situation. In addition, FDA approval for BTE products either through a 510K or IDE/IND/PMA pathway requires the use of a large pre-clinical animal model. However, despite this need, only approximately 60 large animal bone tissue-engineering studies have been published in the past 10 years. Furthermore, NIH has funded only 8% of these studies, and of the 17 bone tissue engineering studies supported by NIH in 2010, only three utilized a large animal model, and none of these used an animal larger than a rabbit. Clearly, increased translation and regulatory approval of BTE therapies will require greater testing in large animal models. We will discuss the current dearth of relevant pre-clinical studies in BTE, and present our work addressing these issues by developing BTE systems (integrated scaffold, growth factor and stem-cell constructs) and testing these systems for realistic clinical applications using the Yorkshire and other swine species as a large pre-clinical animal model. We will detail our work in developing BTE systems for CMF reconstruction and spine fusion in the swine model. Reference Hollister S. J. and Murphy W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. B. (in press).
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Schulz, Joseph M. "The Potential of Induced Pluripotent Stem Cells to Treat and Model Alzheimer’s Disease." Stem Cells International 2021 (May 26, 2021): 1–16. http://dx.doi.org/10.1155/2021/5511630.
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An estimated 6.2 million Americans aged 65 or older are currently living with Alzheimer’s disease (AD), a neurodegenerative disease that disrupts an individual’s ability to function independently through the degeneration of key regions in the brain, including but not limited to the hippocampus, the prefrontal cortex, and the motor cortex. The cause of this degeneration is not known, but research has found two proteins that undergo posttranslational modifications: tau, a protein concentrated in the axons of neurons, and amyloid precursor protein (APP), a protein concentrated near the synapse. Through mechanisms that have yet to be elucidated, the accumulation of these two proteins in their abnormal aggregate forms leads to the neurodegeneration that is characteristic of AD. Until the invention of induced pluripotent stem cells (iPSCs) in 2006, the bulk of research was carried out using transgenic animal models that offered little promise in their ability to translate well from benchtop to bedside, creating a bottleneck in the development of therapeutics. However, with iPSC, patient-specific cell cultures can be utilized to create models based on human cells. These human cells have the potential to avoid issues in translatability that have plagued animal models by providing researchers with a model that closely resembles and mimics the neurons found in humans. By using human iPSC technology, researchers can create more accurate models of AD ex vivo while also focusing on regenerative medicine using iPSC in vivo. The following review focuses on the current uses of iPSC and how they have the potential to regenerate damaged neuronal tissue, in the hopes that these technologies can assist in getting through the bottleneck of AD therapeutic research.
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Lorenz, Mikołaj, Paul Mozdziak, Bartosz Kempisty, and Marta Dyszkiewicz-Konwińska. "Application potential and plasticity of human stem cells." Medical Journal of Cell Biology 7, no. 3 (November 8, 2019): 140–45. http://dx.doi.org/10.2478/acb-2019-0019.
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AbstractSignificant advances have been achieved in the study of stem cells over recent years. Stem cell isolation, their plasticity, differentiation and pre-clinical and clinical applications have undergone a significant study. The objective of this paper is to review the advances in stem cell isolation methods. There are many types of stem cells in the article. Isolation and subsequent differentiation of among others: Human adipose-derived stem cells, cancer stem cells, neural stem cells and mesenchymal stem cells. The subject of Endometrial mesenchymal stromal cells, whose isolation methods are relatively new, was also raised. Attention was paid to the development of preclinical studies using Dental Pulp Stem Cells in various diseases such as Parkinson’s disease or Alzheimer’s disease. Progress in research on the use of stem cells in the treatment of heart attacks, burns, bone injuries and the use of neural stem cells in animal models as an attempt to treat multiple sclerosis has been described.Running title: Potential and plasticity of stem cells
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Puglisi, Caterina, Raffaella Giuffrida, Giuseppina Borzì, Paolo Di Mattia, Anna Costa, Cristina Colarossi, Enrica Deiana, et al. "Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer." Cancers 12, no. 12 (December 7, 2020): 3672. http://dx.doi.org/10.3390/cancers12123672.
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Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are able to predict individual responses to radiotherapy in LARC. CSCs isolated from colorectal cancer biopsies were subjected to in vitro irradiation with the same clinical protocol used for LARC patients. Animal models, generated by CSC xenotransplantation, were also obtained and treated with the same radiotherapy protocol. The results indicate that CSCs isolated from rectal cancer needle biopsies possess an intrinsic grade of sensitivity to treatment, which is also maintained in the animal model. Notably, the specific CSCs’ in vitro and in vivo sensitivity values correspond to patients’ responses to radiotherapy. This evidence suggests that an in vitro radiotherapy response predictivity assay could support clinical decisions for the management of LARC patients, thus avoiding radiation toxicity to resistant patients and reducing the treatment costs.
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Shen, Mengcheng, Thomas Quertermous, Michael P. Fischbein, and Joseph C. Wu. "Generation of Vascular Smooth Muscle Cells From Induced Pluripotent Stem Cells." Circulation Research 128, no. 5 (March 5, 2021): 670–86. http://dx.doi.org/10.1161/circresaha.120.318049.
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The developmental origin of vascular smooth muscle cells (VSMCs) has been increasingly recognized as a major determinant for regional susceptibility or resistance to vascular diseases. As a human material-based complement to animal models and human primary cultures, patient induced pluripotent stem cell iPSC-derived VSMCs have been leveraged to conduct basic research and develop therapeutic applications in vascular diseases. However, iPSC-VSMCs (induced pluripotent stem cell VSMCs) derived by most existing induction protocols are heterogeneous in developmental origins. In this review, we summarize signaling networks that govern in vivo cell fate decisions and in vitro derivation of distinct VSMC progenitors, as well as key regulators that terminally specify lineage-specific VSMCs. We then highlight the significance of leveraging patient-derived iPSC-VSMCs for vascular disease modeling, drug discovery, and vascular tissue engineering and discuss several obstacles that need to be circumvented to fully unleash the potential of induced pluripotent stem cells for precision vascular medicine.
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Grandy, Rodrigo, Rute A. Tomaz, and Ludovic Vallier. "Modeling Disease with Human Inducible Pluripotent Stem Cells." Annual Review of Pathology: Mechanisms of Disease 14, no. 1 (January 24, 2019): 449–68. http://dx.doi.org/10.1146/annurev-pathol-020117-043634.
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Understanding the physiopathology of disease remains an essential step in developing novel therapeutics. Although animal models have certainly contributed to advancing this enterprise, their limitation in modeling all the aspects of complex human disorders is one of the major challenges faced by the biomedical research field. Human induced pluripotent stem cells (hiPSCs) derived from patients represent a great opportunity to overcome this deficiency because these cells cover the genetic diversity needed to fully model human diseases. Here, we provide an overview of the history of hiPSC technology and discuss common challenges and approaches that we and others have faced when using hiPSCs to model disease. Our emphasis is on liver disease, and consequently, we review the progress made using this technology to produce functional liver cells in vitro and how these systems are being used to recapitulate a diversity of developmental, metabolic, genetic, and infectious liver disorders.
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Kunkanjanawan, Tanut, Richard Carter, Kwan-Sung Ahn, Jinjing Yang, Rangsun Parnpai, and Anthony W. S. Chan. "Induced Pluripotent HD Monkey Stem Cells Derived Neural Cells for Drug Discovery." SLAS DISCOVERY: Advancing the Science of Drug Discovery 22, no. 6 (December 27, 2016): 696–705. http://dx.doi.org/10.1177/2472555216685044.
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Huntington’s disease (HD) is a neurodegenerative disease caused by an expansion of CAG trinucleotide repeat (polyglutamine [polyQ]) in the huntingtin ( HTT) gene, which leads to the formation of mutant HTT (mHTT) protein aggregates. In the nervous system, an accumulation of mHTT protein results in glutamate-mediated excitotoxicity, proteosome instability, and apoptosis. Although HD pathogenesis has been extensively studied, effective treatment of HD has yet to be developed. Therapeutic discovery research in HD has been reported using yeast, cells derived from transgenic animal models and HD patients, and induced pluripotent stem cells from patients. A transgenic nonhuman primate model of HD (HD monkey) shows neuropathological, behavioral, and molecular changes similar to an HD patient. In addition, neural progenitor cells (NPCs) derived from HD monkeys can be maintained in culture and differentiated to neural cells with distinct HD cellular phenotypes including the formation of mHTT aggregates, intranuclear inclusions, and increased susceptibility to oxidative stress. Here, we evaluated the potential application of HD monkey NPCs and neural cells as an in vitro model for HD drug discovery research.
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Wu, Nan, Marianne Doorenbos, and Dong Feng Chen. "Induced Pluripotent Stem Cells: Development in the Ophthalmologic Field." Stem Cells International 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/2361763.
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Human induced pluripotent stem cells (iPSCs) are a type of stem cells that can be derived from human somatic cells by introducing certain transcription factors. Induced pluripotent stem cells can divide indefinitely and are able to differentiate into every cell type, which make them viable for transplantation and individual disease modeling. Recently, various ocular cells, including corneal epithelial-like cells, retinal pigment epithelium (RPE) cells displaying functions similar to native RPE, photoreceptors, and retinal ganglion cells, have all been successfully derived from iPSCs. Transplantation of these cells in animal models showed great promise for reversing blindness, and the first clinical trial on humans started in 2013. Despite these promising results, more research is in demand for preventing inadvertent tumor growth, developing precise functionality of the cells, and promoting integration into the host tissue.
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Kraeutler, Matthew J., Justin J. Mitchell, Jorge Chahla, Eric C. McCarty, and Cecilia Pascual-Garrido. "Intra-articular Implantation of Mesenchymal Stem Cells, Part 1." Orthopaedic Journal of Sports Medicine 5, no. 1 (January 1, 2017): 232596711668081. http://dx.doi.org/10.1177/2325967116680815.
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Osteoarthritis (OA) after a partial or total meniscectomy procedure is a common pathology. Because of the high incidence of meniscectomy in the general population, as well as the significant burden of knee OA, there is increasing interest in determining methods for delaying postmeniscectomy OA. Biological therapies, including mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), have been proposed as possible therapies that could delay OA in this and other settings. Several studies in various animal models have evaluated the effect of injecting MSCs into the knee joints of animals with OA induced either by meniscal excision with or without anterior cruciate ligament transection. When compared with control groups receiving injections without progenitor cells, short-term benefits in the experimental groups have been reported. In human subjects, there are limited data to determine the effect of biological therapies for use in delaying or preventing the onset of OA after a meniscectomy procedure. The purpose of this review is to highlight the findings in the presently available literature on the use of intra-articular implantation of MSCs postmeniscectomy and to offer suggestions for future research with the goal of delaying or treating early OA postmeniscectomy with MSCs.
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Zhang, Su-Chun, Xue-Jun Li, M. Austin Johnson, and Matthew T. Pankratz. "Human embryonic stem cells for brain repair?" Philosophical Transactions of the Royal Society B: Biological Sciences 363, no. 1489 (February 23, 2007): 87–99. http://dx.doi.org/10.1098/rstb.2006.2014.
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Cell therapy has been perceived as the main or ultimate goal of human embryonic stem (ES) cell research. Where are we now and how are we going to get there? There has been rapid success in devising in vitro protocols for differentiating human ES cells to neuroepithelial cells. Progress has also been made to guide these neural precursors further to more specialized neural cells such as spinal motor neurons and dopamine-producing neurons. However, some of the in vitro produced neuronal types such as dopamine neurons do not possess all the phenotypes of their in vivo counterparts, which may contribute to the limited success of these cells in repairing injured or diseased brain and spinal cord in animal models. Hence, efficient generation of neural subtypes with correct phenotypes remains a challenge, although major hurdles still lie ahead in applying the human ES cell-derived neural cells clinically. We propose that careful studies on neural differentiation from human ES cells may provide more immediate answers to clinically relevant problems, such as drug discovery, mechanisms of disease and stimulation of endogenous stem cells.
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Tang, Wenchao, Yi Shang, Bin Xiao, Peitong Wen, Ruoyun Lyu, and Ke Ning. "The Cell Research Trends of Asthma: A Stem Frequency Analysis of the Literature." Journal of Healthcare Engineering 2018 (August 23, 2018): 1–10. http://dx.doi.org/10.1155/2018/9363820.
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Objective. This study summarized asthma literature indexed in the Medical Literature Analysis and Retrieval System Online (MEDLINE) and explored the history and present trends of asthma cell research by stem frequency ranking to forecast the prospect of future work. Methods. Literature was obtained from MEDLINE for the past 30 years and divided into three groups by decade as the retrieval time. The frequency of stemmed words in each group was calculated using Python with Apache Spark and the Natural Language Tool Kit for ranking. The unique stems or shared stems of 3 decades were summarized. Results. A total of 1331, 4393, and 7215 records were retrieved from 3 decades chronologically, and the stem ranking of the top 50 were listed by frequency. The number of stems shared with 3 decades was 26 and with the first and last 2 decades was 5 and 13. Conclusions. The number of cell research studies of asthma has increased rapidly, and scholars have paid more attentions on experimental research, especially on mechanistic research. Eosinophils, mast cells, and T cells are the hot spots of immunocyte research, while epithelia and smooth muscle cells are the hot spots of structural cell research. The research trend is closely linked with the development of experimental technology, including animal models. Early studies featured basic research, but immunity research has dominated in recent decades. The distinct definition of asthma phenotypes associated with genetic characteristics, immunity research, and the introduction of new cells will be the hot spots in future work.
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Pisati, Federica, Marzia Belicchi, Francesco Acerbi, Chiara Marchesi, Carlo Giussani, Manuela Gavina, Sophie Javerzat, et al. "Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models." Cancer Research 67, no. 7 (April 1, 2007): 3054–63. http://dx.doi.org/10.1158/0008-5472.can-06-1384.
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Durnaoglu, Serpen, Sermin Genc, and Kursad Genc. "Patient-Specific Pluripotent Stem Cells in Neurological Diseases." Stem Cells International 2011 (2011): 1–17. http://dx.doi.org/10.4061/2011/212487.
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Many human neurological diseases are not currently curable and result in devastating neurologic sequelae. The increasing availability of induced pluripotent stem cells (iPSCs) derived from adult human somatic cells provides new prospects for cellreplacement strategies and disease-related basic research in a broad spectrum of human neurologic diseases. Patient-specific iPSC-based modeling of neurogenetic and neurodegenerative diseases is an emerging efficient tool forin vitromodeling to understand disease and to screen for genes and drugs that modify the disease process. With the exponential increase in iPSC research in recent years, human iPSCs have been successfully derived with different technologies and from various cell types. Although there remain a great deal to learn about patient-specific iPSC safety, the reprogramming mechanisms, better ways to direct a specific reprogramming, ideal cell source for cellular grafts, and the mechanisms by which transplanted stem cells lead to an enhanced functional recovery and structural reorganization, the discovery of the therapeutic potential of iPSCs offers new opportunities for the treatment of incurable neurologic diseases. However, iPSC-based therapeutic strategies need to be thoroughly evaluated in preclinical animal models of neurological diseases before they can be applied in a clinical setting.
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Dai, Sheng, Rong Li, Yan Long, Steve Titus, Jinghua Zhao, Ruili Huang, Menghang Xia, and Wei Zheng. "One-Step Seeding of Neural Stem Cells with Vitronectin-Supplemented Medium for High-Throughput Screening Assays." Journal of Biomolecular Screening 21, no. 10 (September 26, 2016): 1112–24. http://dx.doi.org/10.1177/1087057116670068.
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Human neuronal cells differentiated from induced pluripotent cells have emerged as a new model system for the study of disease pathophysiology and evaluation of drug efficacy. Differentiated neuronal cells are more similar in genetics and biological content to human brain cells than other animal disease models. However, culture of neuronal cells in assay plates requires a labor-intensive procedure of plate precoating, hampering its applications in high-throughput screening (HTS). We developed a simplified method with one-step seeding of neural stem cells in assay plates by supplementing the medium with a recombinant human vitronectin (VTN), thus avoiding plate precoating. Robust results were obtained from cell viability, calcium response, and neurite outgrowth assays using this new method. Our data demonstrate that this approach greatly simplifies high-throughput assays using neuronal cells differentiated from human stem cells for translational research.
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Wu, Haiya, Ling Li, and Xiao Su. "Vagus Nerve throughα7 nAChR Modulates Lung Infection and Inflammation: Models, Cells, and Signals." BioMed Research International 2014 (2014): 1–20. http://dx.doi.org/10.1155/2014/283525.
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Cholinergic anti-inflammatory pathway (CAP) bridges immune and nervous systems and plays pleiotropic roles in modulating inflammation in animal models by targeting different immune, proinflammatory, epithelial, endothelial, stem, and progenitor cells and signaling pathways. Acute lung injury (ALI) is a devastating inflammatory disease. It is pathogenically heterogeneous and involves many cells and signaling pathways. Here, we emphasized the research regarding the modulatory effects of CAP on animal models, cell population, and signaling pathways that involved in the pathogenesis of ALI. By comparing the differential effects of CAP on systemic and pulmonary inflammation, we postulated that a pulmonary parasympathetic inflammatory reflex is formed to sense and respond to pathogens in the lung. Work targeting the formation and function of pulmonary parasympathetic inflammatory reflex would extend our understanding of how vagus nerve senses, recognizes, and fights with pathogens and inflammatory responses.
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Kondziolka, Douglas. "Stem Cell Treatment for Ischemic Stroke Recovery." Seminars in Neurology 41, no. 01 (January 27, 2021): 101–6. http://dx.doi.org/10.1055/s-0040-1722640.
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AbstractThe role of cellular transplantation to promote functional recovery after stroke has been evaluated over the last two decades. Preclinical studies first established the potential for cultured neuronal cells derived from a teratocarcinoma cell line to be tested for safety and efficacy in the treatment of human stroke. In animal models of stroke that caused reproducible learning and motor deficits, injection of neuronal cells resulted in a return of learning behavior, retention time, and motor function. Clinical trials followed. Additional work with cells derived from a bone marrow neuroprogenitor line, fetal cortical stem cells, and other cell sources showed promise in preclinical studies and then these cells were tested in clinical studies. This report reviews the different biological repair approaches using cell implants, discusses clinical trial design and surgical methods, and the current state of research.
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Szubarga, Alicja, Marta Kamińska, Wiktoria Kotlarz, Stefan Malewski, Wiktoria Zawada, Matylda Kuczma, Michal Jeseta, and Paweł Antosik. "Human stem cells – sources, sourcing and in vitro methods." Medical Journal of Cell Biology 9, no. 2 (June 1, 2021): 73–85. http://dx.doi.org/10.2478/acb-2021-0011.
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Abstract Stem cells are an important subject of research, and are increasingly used in the treatment of various diseases. Due to the development of advanced in vitro techniques, they have become an integral part of modern medicine. The sources of human stem cells are primarily bone marrow and adipose tissue, although non – embryonic stem cells are also scattered throughout the body. Notably, recent research has focused on stem cells found in the oral cavity, both in the dental pulp and oral mucosa. Furthermore, isolation of stem cells from umbilical cord blood is also becoming increasingly popular, while wharton’s jelly and amniotic fluid also seem to be an interesting source of stem cells. The safety and efficacy of stem cells use can be established by animal studies, which are a key element of preclinical research. Mouse, rat and pig models allow for testing of stem cell therapies. Recent studies primarily use mesenchymal stem cells such as mouse – adipose derived mesenchymal stem cells and mouse and rat hematopoietic stem cells. Great hope for future therapies is the use of bioengineering to program cells into induced stem cells, which have the biggest ability for differentiation and transdifferentiation, which carries no risk of teratogenesis. Stem cells are used in many areas of medicine, especially in regenerative medicine, with a growing interest in orthopedics and in the treatment of heart failure. Mesenchymal stem cells are the most used stem cell type, which despite their limited ability to differentiate, give great therapeutic results, mainly due to their immunomodulating effect. Recent studies have even shown that the use of mesenchymal stem cells may be useful in the treatment of COVID-19. Moreover, Research on the use of mesenchymal stem cells in the treatment of Crohn’s disease, acute-graft-versus-host disease and type I diabetes are also promising. The aim of the current review is to present and systematize current knowledge about stem cells, their use and related in vitro research. Running title: Research and use of human stem cells
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Choi, S. A., J. H. Lee, K. J. Kim, E. Y. Kim, X. X. Li, A. Lashgari, and M. K. Kim. "380 ISOLATION AND DIFFERENTIATION OF MESENCHYMAL STEM CELLS DERIVED FROM CANINE AMNIOTIC FLUID." Reproduction, Fertility and Development 22, no. 1 (2010): 346. http://dx.doi.org/10.1071/rdv22n1ab380.
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The dog is biologically comparable with humans with respect to stem cell kinetics, haematopoietic demand, and responsiveness to cytokines. The availability of canine mesenchymal stem cells allows for the establishment of the dog as a large animal model for testing the safety and efficacy of mesenchymal stem cells replacement therapy. Large animal models, such as the dog, are invaluable for working out the practicalities of a therapeutic regimen in a complex system and for verifying established mechanistic theories. Therefore, canine stem cells present the potential for unique and exciting biological opportunities. Recent observations also indicate that stem cells derived from second-trimester amniocentesis are pluripotent, capable of differentiating into multiple lineages, including representatives of all 3 embryonic germ layers. Compared with embryonic stem cells, amniotic fluid stem cells can be obtained without destroying embryos, thus avoiding much ethical controversy. The aim of the current study was to investigate adipogenic, osteogenic, and chondrogenic in vitro differentiation potential of canine amniotic fluid-derived mesenchymal stem cells by biological characterization. We successfully isolated and characterized canine amniotic fluid-derived mesenchymal stem cells (cAFS). Expression of stem cell-specific marker OCT3/4, SOX2, and NANOG was confirmed by RT-PCR. Flow cytometric analysis showed that cAFS were positive for CD44, CD29, and CD90 but negative for CD34. Immunocytochemical analysis also showed the expression of alkaline phosphatase, SOX2, SSEA-1, and SSEA-4. Following incubation with specific adipogenic, osteogenic, and chondrogenic agents, cAFS stained positive by Oil Red O and Alizarin Red S, respectively. In conclusion, according to the preview studies on other mammalians, cAFS is an appropriate source of pluripotent stem cells. Here, we demonstrated that cAFS has a high adipogenic, osteogenic, and chondrogenic differentiation potential in vitro. Therefore, amniotic fluid might be a suitable alternative source of stem cells. This study was financially supported by KOSEF (grant #R01-2008-000-21076-0), research fund of Chungnam National University, and the Korean MEST, through the BK21 program for creative research in animal biotechnology.
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Anna, Zadroga, Jezierska-Woźniak Katarzyna, Czarzasta Joanna, Monika Barczewska, Wojtkiewicz Joanna, and Maksymowicz Wojciech. "Therapeutic Potential of Olfactory Ensheathing Cells and Mesenchymal Stem Cells in Spinal Cord Injuries." Stem Cells International 2017 (2017): 1–6. http://dx.doi.org/10.1155/2017/3978595.
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Spinal cord injury (SCI) is a devastating neurological condition that affects individuals worldwide, significantly reducing quality of life, for both patients and their families. In recent years there has been a growing interest in cell therapy potential in the context of spinal cord injuries. The present review aims to discuss and compare the restorative approaches based on the current knowledge, available spinal cord restorative cell therapies, and use of selected cell types. However, treatment options for spinal cord injury are limited, but rehabilitation and experimental technologies have been found to help maintain or improve remaining nerve function in some cases. Mesenchymal stem cells as well as olfactory ensheathing cells seem to show therapeutic impact on damaged spinal cord and might be useful in neuroregeneration. Recent research in animal models and first human trials give patients with spinal cord injuries hope for recovery.
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Hexner, Elizabeth. "The Role of T Cells in Hematopoietic Stem Cell Engraftment." Scientific World JOURNAL 6 (2006): 246–53. http://dx.doi.org/10.1100/tsw.2006.47.
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Much attention has focused on the immune recovery of donor T cells following hematopoietic stem cell transplantation (HSCT). Termed immune reconstitution, a better understanding of the dynamics of the functional recovery of immune cells following HSCT has important implications both for fighting infections and, in the allogeneic setting, for providing antitumor activity while controlling graft-vs.-host disease (GVHD). The immune cells involved in immune reconstitution include antigen-presenting cells, B lymphocytes, natural killer cells, and, in particular, T lymphocytes, the immune cell that will be the subject of this review. In addition, T cells can play an important role in the process of engraftment of hematopoietic stem cells. The evidence for a T cell tropic effect on hematopoietic engraftment is both direct and indirect, and comes from the clinic as well as the research lab. Animal models have provided useful clues, but the molecular mechanisms that govern the interaction between donor stem cells, donor T cells, the host immune system, and the stem cell niche remain obscure. This review will describe the current published clinical and basic evidence related to T cells and stem cell engraftment, and will identify future directions for translational research in this area.
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Zhang, Weiwei, Bin Jiao, Miaojin Zhou, Tao Zhou, and Lu Shen. "Modeling Alzheimer’s Disease with Induced Pluripotent Stem Cells: Current Challenges and Future Concerns." Stem Cells International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/7828049.
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Alzheimer’s disease (AD) is the most prevalent type of dementia and its pathology is characterized by deposition of extracellularβ-amyloid plaques, intracellular neurofibrillary tangles, and extensive neuron loss. While only a few familial AD cases are due to mutations in three causative genes (APP, PSEN1, and PSEN2), the ultimate cause behind the rest of the cases, called sporadic AD, remains unknown. Current animal and cellular models of human AD, which are based on the Aβand tau hypotheses only, partially resemble the familial AD. As a result, there is a pressing need for the development of new models providing insights into the pathological mechanisms of AD and for the discovery of ways to treat or delay the onset of the disease. Recent preclinical research suggests that stem cells can be used to model AD. Indeed, human induced pluripotent stem cells can be differentiated into disease-relevant cell types that recapitulate the unique genome of a sporadic AD patient or family member. In this review, we will first summarize the current research findings on the genetic and pathological mechanisms of AD. We will then highlight the existing induced pluripotent stem cell models of AD and, lastly, discuss the potential clinical applications in this field.
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Crha, Michal, Alois Nečas, Robert Srnec, Jan Janovec, Ladislav Stehlík, Petr Raušer, Lucie Urbanová, Ladislav Plánka, Josef Jančář, and Evžen Amler. "Mesenchymal Stem Cells in Bone Tissue Regeneration and Application to Bone Healing." Acta Veterinaria Brno 78, no. 4 (2009): 635–42. http://dx.doi.org/10.2754/avb200978040635.
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This synoptic study gives a concise overview of current knowledge of bone healing, the role of mesenchymal stem cells in bone tissue regeneration and contemporary possibilities of supporting regeneration of damaged bone. Attention of research concerning the healing of fractures with extensive loss of bone tissue following trauma, the treatment of belatedly healing or non-healing fractures or the healing of segmental bone defects following tumour resection, is focused on development of three-dimensional scaffolds planted with mesenchymal stem cells that might be used for reconstruction of such large bone lesions. Presented are possibilities of transplantation of mesenchymal stem cells combined with biomaterials into bone defects, including the results of our own experimental studies dealing with the use of stem cells in the treatment of damaged tissues of the musculoskeletal system in animal models.
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Ramamoorthi, Murali, Mohammed Bakkar, Jack Jordan, and Simon D. Tran. "Osteogenic Potential of Dental Mesenchymal Stem Cells in Preclinical Studies: A Systematic Review Using Modified ARRIVE and CONSORT Guidelines." Stem Cells International 2015 (2015): 1–28. http://dx.doi.org/10.1155/2015/378368.
Full textAbstract:
Background and Objective. Dental stem cell-based tissue engineered constructs are emerging as a promising alternative to autologous bone transfer for treating bone defects. The purpose of this review is to systematically assess the preclinical in vivo and in vitro studies which have evaluated the efficacy of dental stem cells on bone regeneration.Methods. A literature search was conducted in Ovid Medline, Embase, PubMed, and Web of Science up to October 2014. Implantation of dental stem cells in animal models for evaluating bone regeneration and/or in vitro studies demonstrating osteogenic potential of dental stem cells were included. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to ensure the quality of the search. Modified ARRIVE (Animal research: reporting in invivo experiments) and CONSORT (Consolidated reporting of trials) were used to critically analyze the selected studies.Results. From 1914 citations, 207 full-text articles were screened and 137 studies were included in this review. Because of the heterogeneity observed in the studies selected, meta-analysis was not possible.Conclusion. Both in vivo and in vitro studies indicate the potential use of dental stem cells in bone regeneration. However well-designed randomized animal trials are needed before moving into clinical trials.
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Xie, Zhuo, Zongshan Shen, Peimeng Zhan, Jiayu Yang, Qiting Huang, Shuheng Huang, Lingling Chen, and Zhengmei Lin. "Functional Dental Pulp Regeneration: Basic Research and Clinical Translation." International Journal of Molecular Sciences 22, no. 16 (August 20, 2021): 8991. http://dx.doi.org/10.3390/ijms22168991.
Full textAbstract:
Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.