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1
Che, Mohamad Che Anuar. "Human embryonic stem cell-derived mesenchymal stem cells as a therapy for spinal cord injury." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/7047/.
Повний текст джерелаАнотація:
Traumatic injury to the spinal cord interrupts ascending and descending pathways leading to severe functional deficits of sensory motor and autonomic function which depend on the level and severity of the injury. There are currently no effective therapies for treating such injuries and the adult central nervous system has very limited capacity for repair so that recovery is very limited and functional deficits are usually permanent. Cell transplantation is a potential therapy for spinal cord injury and a range of cell types are being investigated as candidates. Mesenchymal stem cells (MSCs) obtained from bone marrow are one cell type quite extensively studied. When transplanted into animal models of spinal cord injury these cells are reported to affect various aspects of repair and in some cases to improve functional outcome according to behavioural measures. However, the use of these cells has several limitations including the need for an invasive harvesting procedure, variability in cell quality and slow expansion in culture. This project therefore had two main aims: Firstly to investigate whether MSC-like cells closely equivalent to bone marrow derived MSCs could be reliably and consistently differentiated from human embryonic stem cells (hESCs) in order to provide an “off the shelf” cellular therapy product for spinal cord injury and secondly, to transplant such cells into animal models of spinal cord injury in order to, determine whether hESC-derived MSCs replicate or improve on the repair mechanisms reported for bone marrow MSCs.
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Mead, Ben. "Mesenchymal stem cell therapy for traumatic and degenerative eye disease." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/6295/.
Повний текст джерелаАнотація:
Aims The aim of this PhD research project was to investigate the application of dental pulp stem cells (DPSC) as a treatment for traumatic and degenerative eye diseases. The accuracy and reliability of counting retinal ganglion cells (RGC) in radial retinal section was also assessed. Methods Numbers of RGC in radial retinal sections were compared to numbers in retinal wholemounts. DPSC were cultured with RGC and survival and neuritogenesis were quantified. DPSC were also transplanted intravitreally into rat models of optic neuropathy (optic nerve crush) and glaucoma and surviving RGC and regenerated axons were quantified in radial retinal sections. Results Quantifying RGC in radial retinal sections was as reliable and accurate as the current gold standard Thus, retinal wholemounts with Brn3a proved to be the most reliable marker for RGC. DPSC protected RGC from optic nerve crush-/glaucoma-induced death, promoting significant regeneration of RGC axons in the former and preserving visual function (as measured by electroretinography) in the latter. The mechanism of action, as determined in vitro, appeared to be through the secretion of multiple neurotrophic factors (NTF). Conclusions In conclusion, DPSC is a potent cell therapy in the treatment of traumatic and degenerative eye disease.
3
Nili, Ahmadabadi Elham. "Development of a novel mesenchymal stromal cell (MSC) therapy for repairing the cornea." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/122897/1/Elham_Nili%20Ahmadabadi_Thesis.pdf.
Повний текст джерелаАнотація:
This thesis has produced advances in our understanding of the biology and potential clinical application of stem cells to aid the treatment of patients with severe eye injuries. This research evaluated the therapeutic potential of a stem cell (called Mesenchymal Stromal Cells (MSCs)) isolated from the peripheral margin of the cornea, known as the limbus. Firstly, a method for routinely isolation and propagation of human limbal MSCs was optimized. Subsequently, the performance of those cells on a silk fibroin membrane was examined.
4
Nie, Yingjie. "Defective dendritic cells and mesenchymal stromal cells in systemic lupus erythematosus and the potential of mesenchymal stromal cells as cell-therapy." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43278681.
Повний текст джерела
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Wu, Pensée. "Muscular dystrophy cell therapy : an in utero approach using human fetal mesenchymal stem cells." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/4726.
Повний текст джерелаАнотація:
Duchenne muscular dystrophy (DMD) is the most prevalent genetic neuromuscular disorder and affects 1 in 3,500 live male births. Lack of the protein dystrophin in muscle fibres causes permanent muscle damage, is lethal and despite various potential therapeutic strategies aimed at restoring dystrophin expression, has no cure. As DMD affects all skeletal muscles as well as the heart, a systemic treatment would be necessary and in utero stem cell transplantation is a promising way of achieving this. The identification of human fetal mesenchymal stem cells (hfMSC) in early gestation fetal blood offers the prospect of allogeneic or autologous cell therapy, while intrauterine administration would capitalise on ontological opportunities unique to the developing fetus. The aim of the study was to improve hfMSC engraftment and contribution to skeletal muscle fibres following intrauterine transplantation (IUT) in a mouse model of DMD. My project demonstrated that hfMSCs are easily isolated and expandable with the ability to undergo myogenesis in vitro. HfMSCs differentiated into mature myotubes following exposure to galectin-1 conditioned medium, while galectin-1 transduced hfMSCs showed significantly higher expression of myogenic markers compared to non-transduced hfMSCs. Co-culture experiments provided an in vitro model to explore the underlying mechanism for muscle differentiation of hfMSCs following IUT. HfMSCs were able to form chimeric myotubes by fusing with myoblasts isolated from E15 mouse embryos, evidence that they should be able to fuse with developing muscle fibres in vivo. Engraftment and differentiation into muscle fibres of hfMSCs injected intra-peritoneally into E15 mouse embryos in vivo was enhanced by using immunodeficient dystrophic host mice, postnatal muscle injury and additional neonatal hfMSC transplantation following IUT. In conclusion, my thesis supports the use of hfMSC as an attractive source for cell therapy and provides the background for further studies to optimise their engraftment and differentiation to underpin future clinical applications.
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Loebinger, M. R. "Mesenchymal stem cells as vectors for anti-tumour therapy." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/18556/.
Повний текст джерелаАнотація:
Cancer is a leading cause of mortality throughout the world and new treatments are urgently needed. Recent studies suggest that bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate within tumour tissue. This property can be utilised to deliver targeted anticancer therapies. This thesis describes the production of MSCs engineered to express TNF-related apoptosis-inducing ligand (TRAIL), a transmembrane protein that causes selective apoptosis of tumour cells. Human MSCs were transduced with TRAIL and the IRES-GFP reporter gene using a lentiviral vector, under the control of a tetracycline promoter. Transduced and activated MSCs caused lung, breast, squamous, and cervical cancer cell apoptosis in vitro. In vivo, the cells were able to specifically home to tumours and both significantly reduce tumour growth, and eliminate metastatic disease. The data included in this thesis demonstrates for the first time a significant reduction in metastatic tumour burden with frequent eradication of metastases using inducible TRAIL-expressing MSCs. This has a wide potential therapeutic role, which includes the treatment of both primary tumours and their metastases, possibly as an adjuvant therapy in clearing micrometastatic disease following primary tumour resection.
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Ullah, Mujib [Verfasser]. "Molecular characterization of human mesenchymal stem cell differentiation to identify biomarkers for quality assurance in stem cell therapy / Mujib Ullah." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1047579197/34.
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Song, Chao. "Using Mesenchymal Stem Cells As Vehicles for Anit-tumor Therapy." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501407.
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Santos, José Luís da Silva. "Functionalization of dendrimers for improved gene delivery to mesenchymal stem cell." Doctoral thesis, Universidade da Madeira, 2009. http://hdl.handle.net/10400.13/29.
Повний текст джерелаАнотація:
Disease, injury, and age problems compromise human quality of life and continuously motivate the search for new and more efficacious therapeutic approaches. The field of Tissue Regeneration and Engineering has greatly evolved over the last years, mainly due to the combination of the important advances verified in Biomaterials Science and Engineering with those of Cell and Molecular Biology. In particular, a new and promising area arose – Nanomedicine – that takes advantage of the extremely small size and especial chemical and physical properties of Nanomaterials, offering powerful tools for health improvement. Research on Stem Cells, the self-renewing progenitors of body tissues, is also challenging to the medical and scientific communities, being expectable the appearance of new and exciting stem cell-based therapies in the next years. The control of cell behavior (namely, of cell proliferation and differentiation) is of key importance in devising strategies for Tissue Regeneration and Engineering. Cytokines, growth factors, transcription factors and other signaling molecules, most of them proteins, have been identified and found to regulate and support tissue development and regeneration. However, the application of these molecules in long-term regenerative processes requires their continuous presence at high concentrations as they usually present short half-lives at physiological conditions and may be rapidly cleared from the body. Alternatively, genes encoding such proteins can be introduced inside cells and be expressed using cell’s machinery, allowing an extended and more sustained production of the protein of interest (gene therapy). Genetic engineering of stem cells is particularly attractive because of their self-renewal capability and differentiation potential. For Tissue Regeneration and Engineering purposes, the patient’s own stem cells can be genetically engineered in vitro and, after, introduced in the body (with or without a scaffold) where they will not only modulate the behavior of native cells (stem cell-mediated gene therapy), but also directly participate in tissue repair.
Cells can be genetically engineered using viral and non-viral systems. Viruses, as a result of millions of years of evolution, are very effective for the delivery of genes in several types of cells, including cells from primary sources. However, the risks associated with their use (like infection and immunogenic reactions) are driving the search for non-viral systems that will efficiently deliver genetic material into cells. Among them, chemical methods that are promising and being investigated use cationic molecules as carriers for DNA. In this case, gene delivery and gene expression level remain relatively low when primary cells are used. The main goal of this thesis was to develop and assess the in vitro potential of polyamidoamine (PAMAM) dendrimers based carriers to deliver genes to mesenchymal stem cells (MSCs). PAMAM dendrimers are monodispersive, hyperbranched and nanospherical molecules presenting unique characteristics that make them very attractive vehicles for both drug and gene delivery. Although they have been explored for gene delivery in a wide range of cell lines, the interaction and the usefulness of these molecules in the delivery of genes to MSCs remains a field to be explored. Adult MSCs were chosen for the studies due to their potential biomedical applications (they are considered multipotent cells) and because they present several advantages over embryonic stem cells, such as easy accessibility and the inexistence of ethical restrictions to their use. This thesis is divided in 5 interconnected chapters. Chapter I provides an overview of the current literature concerning the various non-viral systems investigated for gene delivery in MSCs. Attention is devoted to physical methods, as well as to chemical methods that make use of polymers (natural and synthetic), liposomes, and inorganic nanoparticles as gene delivery vectors. Also, it summarizes the current applications of genetically engineered mesenchymal stem cells using non-viral systems in regenerative medicine, with special focus on bone tissue regeneration.
In Chapter II, the potential of native PAMAM dendrimers with amine termini to transfect MSCs is evaluated. The level of transfection achieved with the dendrimers is, in a first step, studied using a plasmid DNA (pDNA) encoding for the β-galactosidase reporter gene. The effect of dendrimer’s generation, cell passage number, and N:P ratio (where N= number of primary amines in the dendrimer; P= number of phosphate groups in the pDNA backbone) on the level of transfection is evaluated, being the values always very low. In a second step, a pDNA encoding for bone morphogenetic protein-2, a protein that is known for its role in MSCs proliferation and differentiation, is used. The BMP-2 content produced by transfected cells is evaluated by an ELISA assay and its effect on the osteogenic markers is analyzed through several classical assays including alkaline phosphatase activity (an early marker of osteogenesis), osteocalcin production, calcium deposition and mineralized nodules formation (late osteogenesis markers). Results show that a low transfection level is enough to induce in vitro osteogenic differentiation in MSCs. Next, from Chapter III to Chapter V, studies are shown where several strategies are adopted to change the interaction of PAMAM dendrimers with MSCs cell membrane and, as a consequence, to enhance the levels of gene delivery. In Chapter III, generations 5 and 6 of PAMAM dendrimers are surface functionalized with arginine-glycine-aspartic acid (RGD) containing peptides – experiments with dendrimers conjugated to 4, 8 and 16 RGD units were performed. The underlying concept is that by including the RGD integrin-binding motif in the design of the vectors and by forming RGD clusters, the level of transfection will increase as MSCs highly express integrins at their surface. Results show that cellular uptake of functionalized dendrimers and gene expression is enhanced in comparison with the native dendrimers. Furthermore, gene expression is dependent on both the electrostatic interaction established between the dendrimer moiety and the cell surface and the nanocluster RGD density. In Chapter IV, a new family of gene delivery vectors is synthesized consisting of a PAMAM dendrimer (generation 5) core randomly linked at the periphery to alkyl hydrophobic chains that vary in length and number. Herein, the idea is to take advantage of both the cationic nature of the dendrimer and the capacity of lipids to interact with biological membranes. These new vectors show a remarkable capacity for internalizing pDNA, being this effect positively correlated with the –CH2– content present in the hydrophobic corona. Gene expression is also greatly enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains.
Finally, chapter V reports the synthesis, characterization and evaluation of novel gene delivery vectors based on PAMAM dendrimers (generation 5) conjugated to peptides with high affinity for MSCs membrane binding - for comparison, experiments are also done with a peptide with low affinity binding properties. These systems present low cytotoxicity and transfection efficiencies superior to those of native dendrimers and partially degraded dendrimers (Superfect®, a commercial product). Furthermore, with this biomimetic approach, the process of gene delivery is shown to be cell surface receptor-mediated. Overall, results show the potential of PAMAM dendrimers to be used, as such or modified, in Tissue Regeneration and Engineering. To our knowledge, this is the first time that PAMAM dendrimers are studied as gene delivery vehicles in this context and using, as target, a cell type with clinical relevancy. It is shown that the cationic nature of PAMAM dendrimers with amine termini can be synergistically combined with surface engineering approaches, which will ultimately result in suitable interactions with the cytoplasmic membrane and enhanced pDNA cellular entry and gene expression. Nevertheless, the quantity of pDNA detected inside cell nucleus is always very small when compared with the bigger amount reaching cytoplasm (accumulation of pDNA is evident in the perinuclear region), suggesting that the main barrier to transfection is the nuclear membrane. Future work can then be envisaged based on the versatility of these systems as biomedical molecular materials, such as the conjugation of PAMAM dendrimers to molecules able to bind nuclear membrane receptors and to promote nuclear translocation.Orientadores: Helena Maria Pires Gaspar Tomás e Pedro Lopes Granja
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Yanai, Goichi. "Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy: A Rat Model." Kyoto University, 2015. http://hdl.handle.net/2433/200315.
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11
Chacko, Simi M. "Stem Cell Therapy for Myocardial Infarction: Overcoming the Hypoxic Impediment to Enhance Cell-survival and Engraftment." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243970807.
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Sanders, Douglas N. "Autologous bone marrow-derived mesenchymal stem cell transplantation as a therapy for neuronal ceroid lipofuscinosis." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4830.
Повний текст джерелаАнотація:
Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "August 2007" Includes bibliographical references.
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Zachos, Terri A. "Gene-augmented mesenchymal stem cells in bone repair." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1146076285.
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McMillan, Alexandra. "CONTROLLED PRESENTATION OF GENETIC MATERIAL WITHIN STEM CELL CONDENSATIONS FOR REGULATION OF CELL BEHAVIOR FOR BONE TISSUE ENGINEERING." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1522942029602827.
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Santiago-Torres, Juan E. "Fetal Mesenchymal Stem Cells Achieve Greater Gene Expression in Vitro, but Less Effective Osteoinduction in Vivo than Adult Mesenchymal Stem Cells." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1404561922.
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Murphy, Megan K. "Fibrin microthreads promote stem cell growth for localized delivery in regenerative therapy." Worcester, Mass. : Worcester Polytechnic Institute, 2008. http://www.wpi.edu/Pubs/ETD/Available/etd-090208-143505/.
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Zhang, Wenbiao. "Biochemical modulation and stem cell therapy for irradiated mandible." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43224167.
Повний текст джерела
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Morse, Zachary J. "Dose Response Analysis of Bone Marrow-Derived Mesenchymal Stem Cells for Treatment in Fascial Wound Repair." Youngstown State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1444052561.
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Zhang, Wenbiao, and 張文彪. "Biochemical modulation and stem cell therapy for irradiated mandible." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43224167.
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20
Rafiq, Qasim Ali. "Developing a standardised manufacturing process for the clinical-scale production of human mesenchymal stem cells." Thesis, Loughborough University, 2013. https://dspace.lboro.ac.uk/2134/12335.
Повний текст джерелаАнотація:
Human mesenchymal stem cells (hMSCs) are a promising candidate for cell-based therapies given their therapeutic potential and propensity to grow in vitro. However, to generate the cell numbers required for such applications, robust, reproducible and scalable manufacturing methods need to be developed. To address this challenge, the expansion of hMSCs in a microcarrier-based bioreactor system was investigated. Initial studies performed in T-flask monolayer cultures investigated the effect of key bioprocess parameters such as dissolved oxygen concentration (dO2), the level of medium exchange and the use of serum-free media. 20 % dO2 adversely impacted cell proliferation in comparison to 100 % dO2, whilst FBS-supplemented DMEM was found to be the most consistent and cost-effective cell culture medium despite the advances in serum-free cell culture media. Several microcarriers were screened in 100 mL agitated spinner flasks where Plastic P102-L was selected as the optimal microcarrier for hMSC expansion given the high cell yields obtained, its xeno-free composition and effective harvest capacity. The findings from the initial small-scale studies culminated in the successful expansion of hMSCs on Plastic P102-L microcarriers in a fully equipped 5 L stirred-tank bioreactor (2.5 L working volume), the largest reported volume for hMSC microcarrier culture to date. A maximum cell density of 1.68 x 105 cells/mL was obtained after 9 days in culture; further growth was limited by the low glucose concentration and lack of available surface area. A novel, scalable harvesting method was also developed, allowing for the successful recovery of hMSCs. Importantly, harvested hMSCs retained their immunophenotype, multipotency and ability to proliferate on tissue culture plastic.
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Pesaresi, Martina 1991. "Exogenous expression of chemokine receptors improves mouse mesenchymal stem cell migration towards the degenerating retina." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2019. http://hdl.handle.net/10803/672991.
Повний текст джерелаАнотація:
Retinopathies are a heterogeneous group of conditions that inevitably lead to vision incapacitation and blindness. Currently, they are incurable. Cell therapy has been proposed as a potential solution, but further development and optimization are required. In particular, this study addresses the problem of inadequate migration and integration of transplanted cells into the host tissue. In fact, the majority of the cells transplanted in the eye are unable to reach the injury site, where they are most needed. Hence, we hypothesize that improving cells’ migratory ability could appreciably enhance the therapeutic outcome of transplantation-based strategies.
After identifying the chemokines that are most upregulated during retinal degeneration, we have over-expressed the corresponding receptors on mouse mesenchymal stem cells. Overall, we found that combined exogenous expression of two specific chemokine receptors significantly improves both ex vivo and in vivo migration of mouse mesenchymal stem cells.
The strategy explored in this study provides a way to generate ad hoc engineered stem cells with an increased responsiveness to retina-specific signals. Ultimately, our findings could be integrated with alternative optimization strategies to make stem cell therapy in the eye a feasible and realistic option for the treatment of retinopathies, and for the achievement of visual restoration.Las retinopatías representan un grupo heterogéneo de enfermedades que causan, de forma inevitable, discapacidad visual y ceguera. En la actualidad no se dispone de una cura para estas enfermedades para las que la terapia celular podría ser una solución válida, en el caso de que ésta pudiera ser mejorada y optimizada. El presente estudio enfrenta el problema de la escasa e inadecuada migración de las células trasplantadas en el tejido diana. De hecho, la mayoría de las células trasplantadas en el globo ocular no consiguen llegar allí donde se las requiere; donde se encuentra la lesión. Por este motivo, se plantea la hipótesis de que mejorar la capacidad migratoria de las células podría resultar en una mejora substancial del resultado terapéutico de los trasplantes celulares. Después de identificar las quimiocinas más expresadas durante la degeneración de la retina, se ha procedido a sobre-expresar los receptores correspondientes en células madre mesenquimales de ratón. En general, los resultados obtenidos indican que la expresión exógena combinada de dos receptores específicos de quimiocinas mejoran significativamente la migración de células madre mesenquimales, tanto ex vivo como in vivo. La estrategia desarrollada en este estudio proporciona una forma de generar células madre con una mayor capacidad de respuesta a señales específicas de la retina. Tanto es así, que los hallazgos que en él se detallan podrían integrarse con otras estrategias de optimización, de forma que la terapia con células madre sea una opción factible y realista para el tratamiento de retinopatías.
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Mikail, Philemon. "Translational Predictive Model for Heart Failure Recovery in LVAD Patients Receiving Stem Cell Therapy." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/613398.
Повний текст джерелаАнотація:
Introduction: Heart failure remains a major public health problem, with recent estimates indicating that end-stage heart failure with two-year mortality rates of 70-80% affects over 60,000 patients in the US each year. Medical management can be used but success declines for patients with end stage heart failure. Although cardiac transplantation is optimal, less than 2500 cardiac transplants are performed annually due to the severely limited supply of donor organs. Mechanical circulatory support (MCS) devices are now routinely used to bridge patients with end-stage heart failure who become critically ill until a donor heart is available. The use of stem cell therapy to treat heart failure has been gaining significant ground in recent years, specifically due to its regenerative properties, and both animal and human models have shown significant improvements in ventricular mass, ejection fraction, vascularization, wall thickness, and infarct size reduction. Using the patients' HeartWare HVAD device diagnostics, we were able to acquire our response variable; pulsatility. Pulsatility is a variable measure of the differential between minimum and maximum flow and is dependent on device motor speed, power, current, and fluid viscosity. This measurement is important as it relates to the contractility of the heart and could potentially be used as an end point in determining when a patient is healthy enough to have their HVAD explanted. We set out to develop a low cost and effective predictive model to determine amniotic mesenchymal stem cell's ability to repair compromised cardiac tissue of patients using the Total Artificial Heart (TAH) and Donovan Mock Circulation Tank (DMC). Methods: Predictive modelling was performed using the TAH and DMC. The system was set to a range from critical heart failure to a normal operating conditions through the variation of preload, afterload, and ventricular drive pressures with the intent of comparing the results to our patient population. Patients (n=7, 3 dilated, 4 ischemic) received intravenous and intra-myocardial injections of a heterogeneous amniotic mesenchymal stem cells mixture and liquid matrix (MSCs+LM) at HVAD implant. Groups were analyzed based on treatment; control (HVAD only, n=7) versus stem cells (HVAD + MSCs+LM). HeartWare log files were acquired from patients' devices and analyzed in SAS and Matlab. Results from the patient study were compared to the predictive model to determine levels of stem cell response. Results: Pulsatility was found to increase with left drive pressure and afterload. Lower drive pressures resulted in a drop off in pulsatility at higher afterloads while higher drive pressures were able to compensate for any afterload. Pulsatility also increased with preload but lower drive pressures were unable to fully eject at the highest preloads, resulting in a reduced pulsatility. We observed the effects of the stem cell injections on pulsatility and found that patients receiving therapy demonstrated statistically significant increases in pulsatility at 15-20 (p=.0487), 25-30 (p=.0131), 35-40 (p=.0333), and 75-80 (p=0.0476) days post implant. At minimum, when comparing the patient results to the in vitro model, the therapy resulted in a progression from end stage HF conditions to medium cardiac function conditions. At maximum, the therapy resulted in a progression from end stage HF to normal healthy operating cardiac function. Conclusions: Stem cells demonstrated a significantly increased rate of change in pulsatility within the first 40 days and at 80 days post implant when compared to control. They also demonstrated progression from end stage HF to normal healthy cardiac function at two time periods (Days 40, 90). These results justify expansion of the study to encompass a larger patient population to verify the results of the in vitro model to predict cardiac regeneration with multiple functional status indicators.
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Connick, Peter Vincent. "Autologous mesenchymal stem cells as a neuroprotective therapy for secondary progressive multiple sclerosis." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648163.
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Nie, Yingjie, and 聶瑛潔. "Defective dendritic cells and mesenchymal stromal cells in systemic lupus erythematosus and the potential of mesenchymal stromal cells ascell-therapy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43278681.
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Shafiee, Abbas. "Isolation and characterisation of primitive stem cell populations from placenta." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/95086/1/Abbas_Shafiee_Thesis.pdf.
Повний текст джерелаАнотація:
Cardiovascular diseases (CVD) are the leading cause of death in developed societies. Vascular stem cells (VSCs) have been proposed as a cell population with regenerative potential for CVD. However, the in vivo ontogeny of VSCs remains controversial. In current study, we have isolated VSCs from the human term placenta and characterized in vivo cell populations which give rise to different stem cells. Furthermore, a novel hierarchy among vascular cells as well as their physiological localization were established. Collectively, this is an important finding for both developmental biology and cell-based therapy and may potentially provide an avenue for future cell therapies.
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Qin, Hong. "Co-culture of hepatocytes with mesenchymal stem cells for cellular therapy in liver disease." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/coculture-of-hepatocytes-with-mesenchymal-stem-cells-for-cellular-therapy-in-liver-disease(7d1b05f4-343c-4f98-93fa-ae23a86788c2).html.
Повний текст джерелаАнотація:
A major hurdle facing current hepatocyte transplantation practice is the marginal quality of isolated hepatocytes. Previous studies showed that mesenchymal stem cells (MSCs) could maintain morphology and improve liver-specific metabolism of co-cultured hepatocytes. The present work aimed to optimise the MSCs co-culture system by testing adipose tissue (AT), bone marrow, and umbilical cord-derived MSCs at predefined seeding ratios. Liver-specific metabolism and apoptosis assays were performed to investigate hepatotrophic and antiapoptotic effects of MSCs co-culture. Indirect co-culture was established to investigate the role of paracrine factors in hepatotrophic effect of MSCs co-culture. Hypoxia-preconditioned (HPc) MSCs were co-cultured with hepatocytes to investigate potentiative effect of HPc induction. Intracellular reactive oxygen species (ROS) activity quantitation and antagonisation experiments were performed to investigate whether HPc potentiated MSCs co-culture by an intracellular ROS-dependent mechanism. Tumour necrosis factor alpha (TNF-α), transforming growth factor beta1 (TGF-β1), extracellular collagen, and apoptosis- associated caspase and BAX/BCL-2 signalling pathways were analysed to investigate the contribution of soluble factors, extracellular collagen, and gene signalling to the hepatotrophic effects of MSCs co-culture and potentiative effect of HPc induction. All the three types of MSCs exhibited a similar hepatotrophic effect, with a comparable effect even in low-density AT-MSCs co- culture. Hepatotrophic and antiapoptotic effects of MSCs showed a cell contact dependent manner, and HPc potentiated MSCs co-culture by a cell-contact intracellular ROS-dependent mechanism. Decreased hepatocyte autocrine TNF-α, increased MSC autocrine TGF-β1, and enhanced MSCs deposition of extracellular collagen contributed to the hepatotrophic effects of MSCs co-culture and potentiative effect of HPc induction, with downregulated expression of proapoptotic CASP9, BAX, and BID and upregulated expression of antiapoptotic BCL-2. It is concluded that synergistic effects of cell contact, intracellular ROS-dependent soluble factors, extracellular matrix, and apoptosis- associated signalling in MSCs co-culture contribute to hepatotrophic effect and HPc-induced potentiative effect. Co-transplantation with MSCs should improve therapeutic effects of HCT by enhancing survival and metabolism of co-transplanted hepatocytes.
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Li, Xiang, and 李想. "Effects of human mesenchymal stem cells on cigarette smoke-induced lung damage." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49618209.
Повний текст джерелаАнотація:
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by persistent airway obstruction that is only partially reversible. It is the fourth leading cause of death and is predicted to be the third by 2030. The progression of the disease involves chronic inflammation, oxidative stress, excess protease activity, increased lung cell apoptosis and accelerated lung aging, but the exact pathogenesis is still unclear. The major cause of COPD is cigarette smoking(CS). Although COPD is associated with increasing social and economical burden, there have been few advances in pharmacological therapy of COPD.
Mesenchymal stem cells (MSCs) are fibroblast-like multipotent stem cells which can be isolated from a broad range of sources including bone marrow (BM) and adipose tissue. Administration of BM-derivedMSCs (BM-MSC) or adipose tissue-derived MSCs was reported to attenuate CS-induced emphysema in murine models. Induced pluripotent stem cell-derived MSC (IPSC-MSC) are MSCs differentiated from induced pluripotent stem cells(IPSCs), which are pluripotent cells generated by somatic cell reprogramming in vitro. IPSC-MSCs have several advantages over BM-MSC, including more abundant sources and high capacity of doubling without loss of differentiation potency.
A general exploration and comparison on the effects of human IPSC-MSC and BM-MSC treatments were carried out in a 56-day CS-exposed rat model. Compared to BM-MSC, IPSC-MSC showed a higher capacity to reside in lung tissue. The two treatments shared similar efficacy to attenuate CS-induced lung cell apoptosis, to restore CS-induced reduction of lungIL-10and to alleviate CS-induced elevation of systemic TGF-β1. In addition, IPSC-MSC was found to cause reduction in CS-induced elevation of systemic oxidative stress and reversal of CS-induced reduction of lung adiponectin.
Furthermore, in order to understand the possible paracrine mechanism involved, human airway epithelial cells were treated with IPSC-MSC or BM-MSC-conditioned medium in a cell culture system in the presence of cigarette smoke medium (CSM). Potentiation rather than attenuation of CSM-induced release of pro-inflammatory cytokine IL-8, MCP-1 and IL-6 was observed with IPSC-MSC or BM-MSC conditioned medium. It is currently unknown whether cultured IPSC-MSCs or BM-MSCs will release pro-inflammatory mediators into the conditioned medium or not.
In order to study CS-induced oxidative stress and inflammation in a short time frame, anacute (5-day) CS-exposed rat model was established in juvenile and adult groups. An age-dependent alteration of CS-induced oxidative and inflammatory responses was demonstrated in this model.
In summary, our in vivo rat model provides a platform for elucidating the effects of stem cell treatment in CS-induced oxidative stress and inflammation, leading to lung damage. Our findings suggest that treatment of IPSC-MSC or BM-MSC might be able to slow down CS-induced disease progression, possibly through anti-oxidant, anti-inflammatory and anti-apoptotic properties. However, caution should be taken as our in vitro data revealed that conditioned medium from MSCs may provoke pro-inflammatory responses. Further studies on the regulation of the activity of MSCs in vivo will be needed before developing IPSC-MSC into cell therapies for COPD to halt the progression over time.published_or_final_version
Medicine
Master
Master of Philosophy
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Morris, Timothy J. "Exploring the improvement of human cell cryopreservation." Thesis, Loughborough University, 2015. https://dspace.lboro.ac.uk/2134/19279.
Повний текст джерелаАнотація:
Regenerative medicine is an emerging technology and with hundreds of cell therapies currently in clinical trials there is a need to expand the limited knowledge related to their storage, shipment and preservation. The most widely used medium for human cell cryopreservation is 10%wt dimethyl sulfoxide (DMSO) in serum. However given its potential toxicity, DMSO usage is a key issue in cryopreservation. Methods specify the need to reduce cell exposure time to DMSO above 0°C as much as possible but the maximum amount of time cells can be exposed to DMSO to prevent a detrimental effect needs to be clarified. There are also regulatory issues and concerns with the xenotoxicity, ethics and supply of the other core component in the standard cryomedia formulation: Foetal Bovine Serum (FBS). Developing a viable alternative to FBS is crucial. In cryobiology literature thawing appears poorly understood. A stable process is as vital as freezing to prevent injury to cells. Protocols are currently too vague for cell therapy regulation and need improvement. The time dependent DMSO cytotoxicity was evaluated by overexposing cells to DMSO during and/or after cryopreservation. A broad investigation found that after 1 hour overexposure post thaw viability of human mesenchymal stem cells (hMSCs) was reduced from 96.3±0.6% to 74.1±4.0% and the co-expression of five key hMSC markers was changed from 97.9±1.3% to 68.3±2.6%. This significant change could cause indicate a change in product efficacy and affect patient health, to prevent this, DMSO exposure must be kept to below 1 hour. A range of alternative vehicle solutions were screened and human platelet lysate (hPL) investigated as an alternative. In depth experimentation with hPL as a cryopreservation vehicle solution and culture supplement (in place of FBS) found it to be a worthy, statistically similar alternative. With no xenological or ethical concerns, lower costs than other serum-free alternatives hPL could allow for a move away from xenological components. A heat transfer model was developed and determined that 720J is required to thaw a vial. Using the heat transfer model and additional factors such as pre-thaw stabilisation and on thaw dilution, a two-stage experiment found that the current standard process (warming in a 37°C waterbath) within the current paradigm of a 1.8mL cryovial is optimal but further work is required to define the process for scaled-up product.
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Perruisseau-Carrier, Claire. "Neuronal commitment of Umbilical Cord Mesenchymal Stem Cells for brain regenerative medicine." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10192.
Повний текст джерелаАнотація:
De nos jours, aucune prévention ou aucun remède efficace n'existe pour guérir les maladies du cerveau humain. Les cellules souches représentent un grand espoir pour la réparation et la régénération des tissus neuraux endommagés. L'objectif de cette thèse est d'évaluer la capacité des cellules souches du cordon ombilical humain (hUC MSCs) à se différencier en neurones, pour une thérapie cellulaire appliquée au cerveau. Nous avons isolé, multiplié et caractérisé les hUC MSCs naïves à l'échelle des gènes et des protéines. Ensuite, les e_ets sur l'expansion des hUC MSCs et leur différenciation neuronale de différents paramètres ont été évalués par qPCR et marquages immunologiques principalement: milieux et matrices de culture, oxygénation, culture en 3D, ainsi que divers facteurs et molécules tels que les microARNs. Les résultats montrent que les hUC MSCs prolifèrent mieux sans sérum et en conditions de normoxie du cerveau (1-5 % O2). Les hUC MSCs naïves semblent préparées à devenir des neurones à l'échelle des gènes et des protéines, mais pas suffisamment pour supporter leur complète différenciation. L'introduction de microARNs requiert des améliorations pour réguler efficacement les voies de signalisation des hUC MSCs. Au cours de cette étude, nous avons identifé les paramètres favorisant l'expansion des hUC MSCs dans des conditions compatibles avec la clinique. Cependant, une question reste ouverte: les hUC MSCs sont-elles capables de vraie transdifferentiation en neurones fonctionnels malgré les controverses? Des recherches supplémentaires sont nécessaires, mais cette étude constitue une première étape vers l'utilisation des hUC MSCs en médecine régénératrice du cerveauNowadays, no effective prevention or cure of human brain diseases is available. Stem cells hold great promise for the repair and regeneration of damaged neural tissues. This thesis aims to evaluate the potency of human umbilical cord mesenchymal stem cells (hUC MSCs) to be committed to the neuronal lineage, for brain cell-based therapy. To achieve this goal, naive hUC MSCs were isolated, expanded, and characterized at the gene and protein level, while particularly focusing on the neuronal lineage and clinical-grade culture conditions. Then, several parameters were investigated for hUC MSCs proliferation and neuronal commitment, including media, coatings, 3D culture, hypoxia, chemicals and molecules. Growth curves drawings, qPCRs, and immunostainings were used among other methods for identifying the best conditions for hUC MSCs expansion, differentiation, culture in 3D, and microRNAs delivery. The results indicate that hUC MSCs better proliferate in serum-free media and brain's normoxia condition (1-5 % O2). Naive hUC MSCs appear primed for neuronal fate at gene and protein level, but not su_ciently to support their neuronal di_erentiation. microRNAs delivery requires further improvement to efficiently promote neuronal signaling pathways in hUC MSCs. Along this study we identified the best parameters for hUC MSCs expansion in clinical-grade conditions. However, a question still remains: are hUC MSCs capable of full transdifferentiation towards functional neurons despite all controversies? Additional work is needed, but this study is a first step towards answering this question, bringing more clues to make transplantation of hUC MSCs for brain regenerative medicine closer
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Heathman, Thomas R. J. "Developing a process control strategy for the consistent and scalable manufacture of human mesenchymal stem cells." Thesis, Loughborough University, 2015. https://dspace.lboro.ac.uk/2134/22174.
Повний текст джерелаАнотація:
Human mesenchymal stem cells (hMSCs) have been identified as a promising cell-based therapy candidate to treat a number of unmet clinical indications, however, in vitro expansion will be required to increase the available number of cells and meet this demand. Scalable manufacturing processes, amenable to closed, single-use and automated technology, must therefore be developed in order to produce safe, effective and affordable hMSC therapies. To address this challenge, a controlled serum-free end-to-end microcarrier process has been developed for hMSCs, which is amenable to large-scale manufacture and therefore increasing economies of scale. Preliminary studies in monolayer culture assessed the level of variability in growth between five hMSC donors, which was found to have a variance of 25.3 % after 30 days in culture. This variance was subsequently reduced to 4.5% by the development of a serum-free monolayer culture process with the maintenance of critical hMSC characteristics and an increased number of population doublings. In order to transfer this into a scalable system, the serum and serum-free expansion processes were transferred into suspension by the addition of plastic microcarriers in 100 mL spinner flasks without control of pH or dissolved oxygen (DO). This achieved a maximum cell density of 0.08 ± 0.01 · 106 cells.mL-1 in FBS-based medium, 0.12 ± 0.01 · 106 cells.mL-1 in HPL-based medium and 0.27 ± 0.03 · 106 cells.mL-1 in serum free medium after six days. In order to drive consistency and yield into the manufacturing process, a process control system was developed for the FBS-based microcarrier expansion process in a 100 mL DASbox bioreactor platform to control DO, pH, impeller rate and temperature. Reduced impeller rates and DO concentrations were found to be beneficial, with a final cell density of 0.11 ± 0.02 · 106 cells.mL-1 and improved post-harvest outgrowth and colony-forming unit (CFU) potential compared to uncontrolled microcarrier and monolayer culture. This controlled bioreactor expansion process was then applied to the previously developed serum-free microcarrier process, eventually achieving a final cell density of 1.04 ± 0.07 · 106 cells.mL-1, whilst retaining key post-harvest hMSC characteristics. Following the controlled serum-free expansion and harvest of hMSCs, a downstream and cryopreservation process was developed to assess the impact of prolonged holding times and subsequent unit-operations on hMSC quality characteristics. This showed that hMSCs are able to maintain key characteristics throughout the entire end-to-end process, demonstrating their potential for commercial scale manufacture.
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Wright, Elizabeth Joanne. "GLP-1 CellBead therapy for the prevention of left ventricular dysfunction in pigs." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/glp1-cellbead-therapy-for-the-prevention-of-left-ventricular-dysfunction-in-pigs(740704bb-46f1-44af-8eb2-22117a7efd05).html.
Повний текст джерелаАнотація:
Background: Stem cells are a promising therapy for regeneration following myocardial infarction (MI). Another therapy currently under investigation for MI is glucagon-like peptide-1 (GLP-1), a natural incretin hormone that has cardio-protective properties, although a short half-life in vivo. GLP-1 CellBeads are a novel therapy, combining stem cells and GLP-1. Human mesenchymal stem cells (MSCs) were immortalised, engineered to secrete a fusion protein of GLP-1 and encapsulated in alginate. We have previously demonstrated that GLP-1 CellBeads significantly reduce infarct size and improve ejection fraction post-MI, but the underlying mechanisms are unclear. The therapy was assessed in an in vivo pig MI model and an in vitro cardiomyocyte ischaemia model. Methods: GLP-1 CellBeads were delivered to coronary artery branches in pigs, creating micro-infarcts, as determined by echocardiography. Cell-free beads (Beads) and CellBeads containing hMSCs without GLP-1 (Beads-MSC) were delivered as controls (n=3-5/group). Pigs were sacrificed one and four weeks post-MI. Tissue was analysed for: apoptosis, collagen, cardiomyocyte cross sectional area and myofibroblasts. The localised response around the beads was also measured using immunohistochemistry. Atomic force microscopy (AFM) was used to examine the ultra-structure of the collagen scar. The expression profiles of genes involved in collagen remodelling were measured using qRT-PCR. Viability of MSCs was measured using GFP-tagging and confirmed using qRT-PCR. To examine effects on apoptosis in vitro, human adult cardiomyocytes underwent ischaemia for 1 hour before incubation with: media conditioned with MSCs or MSC+GLP-1, GLP-1, Exendin-4 or media. Apoptosis and viability were measured at 24 and 48 hours respectively. Results: In the in vivo pig model, significant increases in apoptosis were observed in the infarct of all groups one week post-MI, with no differences between treatments. Despite decreased numbers of myofibroblasts, significantly more collagen was observed in MSC treated groups, with increased collagen fibril periodicity and a more organised collagen scar. The altered scar structure was reflected in differences in gene expression between groups, with an accelerated healing response in the MSC groups. However, significantly fewer myofibroblasts were observed in the MSC treated groups. Viability of MSCs was confirmed up to four weeks post-infusion, with GLP-1 secretion confirmed up to one week. In the in vitro ischaemia model, MSC+GLP-1 conditioned media significantly reduced cardiomyocyte apoptosis 24 hours post-ischaemia, compared to media alone. All agonists (GLP-1, MSC media and MSC+GLP-1 media) significantly improved viability compared to media alone 48 hours post-ischaemia. Conclusions GLP-1 CellBeads have a beneficial effect on healing following MI by significantly decreasing infarct size and improving ejection fraction post-MI. these benefits are associated with decreased cardiomyocyte apoptosis and altered collagen scar formation. The CellBeads act as local hubs for regeneration and are viable up to one month post-infusion. The effects observed are due to a combination of the GLP-1 and paracrine factors released from the hMSCs.
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Knoop, Kerstin. "Molecular imaging and radionuclide therapy in non-thyroidal tumors after mesenchymal stem cell- mediated sodium/iodide symporter (NIS) gene transfer." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-178550.
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Pasian, Ana Carolina Picolo [UNESP]. "Contribuição do led 850 nm, pulsátil, na cultura de célula-tronco mesenquimal." Universidade Estadual Paulista (UNESP), 2018. http://hdl.handle.net/11449/153664.
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A medicina regenerativa é uma área em crescente expansão no Brasil e no mundo, a qual procura ampliar a capacidade natural de regeneração dos tecidos através da utilização de células, fatores de proliferação e biomateriais. Um dos ramos da medicina regenerativa é a terapia celular, vertente que utiliza células-tronco, visando a substituição de tecidos funcionalmente ou estruturalmente lesados, apresentando um caráter terapêutico. Na medicina LASERs e LEDs vem sendo estudados como ferramenta terapêutica, mostrando possuir capacidade bioestimulatória. Este campo é caracterizado por uma variedade de metodologias, que são utilizadas em uma gama considerável de aplicações. Na técnica de fotoestimulação, utiliza-se a luz para ativar moléculas e funções celulares, apresentando o potencial de afetar a proliferação e diferenciação e o metabolismo da célula, estimulando a fosforilação oxidativa e podendo reduzir a resposta inflamatória local. Entretanto para que essa resposta ocorra, inúmeros trabalhos afirmam sobre a importância da seleção de um comprimento de onda ideal, uma vez que a utilização de um comprimento inapropriado pode acarretar em resultados contrários aos esperados, como a bioinibição. Diante destes achados o presente trabalho propôs-se a avaliar a ação do LED 850nm, no regime pulsátil, nas doses de 3, 5 e 10J/cm² na cultura de célula-tronco mesenquimal (CTM) com Soro Fetal Bovino (SFB) e com Hormônios derivados de plaquetas (HDP), e na cultura de células de Linfoma linfoblástico tipo B, RAJI Cells na dose de 10J/cm². Em ambos experimentos de exposição a luz, o comprimento de onda 850 nm inibiu a proliferação celular. Na cultura de CTM o LED tornou o desdobramento celular mais lento e acarretou na diminuição da confluência celular, especialmente nas doses de 5 e 10J/cm². Na cultura de linfoma Linfoblástico tipo B, em apenas 1 semana de exposição o mesmo comportamento de bioinibição foi encontrado na dose de 10J/cm². O grupo não tratado apresentou 7,0 X 10 5 células, em média, por frasco enquanto que as células submetidas à irradiação sofreram diminuição do tempo de desdobramento sendo a concentração destas de 4,2X105 , em média, por frasco.
Regenerative medicine is a promising growing area worldwide, with the aim of restore and regenerate tissues and whole organs through the use of cells, proliferation factors and biomaterials. One branch of regenerative medicine is cell therapy, that uses stem cells, aiming at the substitution of functionally or structurally damaged tissues, presenting therapeutic fature. LASERs and LEDs are available as therapeutic tools, showing biostimulating ability. The photo-stimulation technique uses light to activate molecules and cellular functions, presenting potential to affect proliferation, cell differentiation and metabolism, stimulating oxidative phosphorylation and reducing the local inflammatory response. Data shows the importance of selecting an ideal wavelength, such as the use of an inappropriate choice, can lead to undisered results, such as bioinhibition. In the present work, we evaluated the action of LED 850nm, pulsatile, at the doses of 3, 5 and 10J/cm² in mesenchymal stem cells (CTM) with Bovine Fetal Serum (FBS) and with derived platelets – Hormones (HDP) and B-cell lymphoblastic cell culture, 10J /cm2 , RAJI cells. In all light exposure experiments, wavelength of 850 nm inhibited cell proliferation. CTM culture, LED had a low proliferation rate, resulting in a decrease in cellular confluence, especially at 5 and 10J/cm2 . Lymphoblastic lymphoma type B cells, in only one week of exposure presente the same behavior of bioinhibition at 10J/cm2 . The control group had 7.0 x 105 cells on per vial, while cells subjected to irradiation underwent the unfolding time at a concentration of 4.2 x 105 on average per vial.
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Chan, Jerry Kok Yen. "Human fetal mesenchymal stem cells for intrauterine cellular/gene therapy using muscular dystrophy as a model." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441391.
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Ettey, Thywill. "An Investigation of Collagen, Platelet-Rich Plasma and Bone Marrow Derived Mesenchymal Stem Cells on Achilles Tendon Repair in a Rat Model." Youngstown State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1559127777520856.
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Hoogduijn, Martin J., F. Popp, R. Verbeek, Mojgan Masoodi, Anna Nicolaou, C. Baan, and M.-H. Dehlke. "The immunomodulatory properties of messenchymal stem cells and their use for immunotherapy." Elsevier, 2010. http://hdl.handle.net/10454/4576.
Повний текст джерелаАнотація:
noThere is growing interest in the use of mesenchymal stem cells (MSC) for immune therapy. Clinical trials that use MSC for treatment of therapy resistant graft versus host disease, Crohn's disease and organ transplantation have initiated. Nevertheless, the immunomodulatory effects of MSC are only partly understood. Clinical trials that are supported by basic research will lead to better understanding of the potential of MSC for immunomodulatory applications and to optimization of such therapies. In this manuscript we review some recent literature on the mechanisms of immunomodulation by MSC in vitro and animal models, present new data on the secretion of pro-inflammatory and anti-inflammatory cytokines, chemokines and prostaglandins by MSC under resting and inflammatory conditions and discuss the hopes and expectations of MSC-based immune therapy.
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André, Emilie. "Combination of nano and microcarriers for stem cell therapy of Huntington's disease : new regenerative medicine strategy." Thesis, Angers, 2015. http://www.theses.fr/2015ANGE0047/document.
Повний текст джерелаАнотація:
La combinaison de biomatériaux et cellules souches, a pour but de protéger des cellules endommagées et de ralentir la progression des maladies neurodégénératives, comme la maladie de Huntington (MH). Les cellules souches mésenchymateuses et particulièrement une sous-population, les cellules MIAMI, ont déjà démontré leur efficacité dans la maladie de Parkinson. Il est cependant essentiel d’améliorer leur différenciation neuronale, leur survie et évaluer leur sécrétome. L’objectif principal de ce travail fut de proposer une stratégie innovante de médecine régénératrice pour la MH associant cellules souches, nano et micro médecines. Pour l’évaluer, un nouveau modèle animale ex vivo de la MH a été mis en place. Nous avons ensuite développé et optimisé deux nano-vecteurs, des nanocapsules lipidiques et des nanoparticules solides de SPAN, et les avons associés à un inhibiteur de REST qui est un facteur de transcription qui empêche la différenciation neuronale. La transfection de ce siREST a montré une amélioration du phénotype neuronal. Ces cellules ainsi modifiées furent ensuite induites vers un phénotype GABAergic grâce à des facteurs de croissance. Puis elles ont été associées à un support 3D, les microcarriers pharmacologiquement actif (MPA) permettant une meilleure intégration des cellules après greffe. Les MPA sont des microsphères ayant une surface biomimétique de laminine et libérant de façon contrôlée un facteur trophique le « brain derived neurotrophic factor » (inducteur d’un phénotype neuronal et neuro-protecteur). Des résultats prometteurs ont été obtenus, encourageant à continuer l’évaluation de cette stratégie in vivo dans des modèles génétiques de la MHThe combination of biomaterials and stem cells aims to protect damaged cells and slow the progression of neurodegenerative diseases such as Huntington's disease(HD). Mesenchymal stem cells, particularly a subpopulation known as MIAMI cells, have already demonstrated their effectiveness in Parkinson's disease. However, it is essential to improve their neuronal differentiation, survival, and to assess their secretome. The main objective of this work was to propose an innovative regenerative medicine strategy for HD by combining stemcells, micro and nano medicines. To perform this assessment, a new ex vivo animal model of HD has been set up. We then developed and optimized two nanovectors,lipid nanocapsules and solid SPAN nanoparticles,carrying an inhibitor of REST a transcription factor, which prevents neuronal differentiation. The transfection of this siREST showed an improvement in the neuronal phenotype. These modified cells were then induced into a GABAergic phenotype through growth factors. They were then associated with a 3D support, the pharmacologically active microcarriers (PAM) allowing a high rate of engraftment. The PAM are microspheres which have a biomimetic surface of laminin and release a trophic factor BDNF, brain derived neurotrophic factor (inducer of a neural phenotype and neuroprotective) in a controlled manner. Promising results were obtained, further encouraging continuing the evaluation of this strategy in vivo in genetic models of HD
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Robinson, Nathalie J. "Low-temperature pausing : an alternative short-term preservation method for use in cell therapies." Thesis, Loughborough University, 2016. https://dspace.lboro.ac.uk/2134/25183.
Повний текст джерелаАнотація:
With encouraging advancements in cell therapies, there is a requirement for an effective short-term cell preservation method, enabling time for quality assurance testing and transport to their clinical destination. This project aims to pause cells at ambient temperatures, whilst maintaining viability and function post-preservation. Ambient cell preservation bypasses ice crystal exposure and toxic solute concentrations experienced with cryogenic storage. Storage in ambient conditions also avoids use of toxic cryoprotectants and aims to greatly reduce costs and reliability on specialist machinery. Early work used HOS TE85 cells (derived from an osteosarcoma) as a model. When atmospheric factors were controlled, HOS TE85 cells demonstrated effective recovery in terms of morphology, membrane integrity (viability >90%) and fold growth expansion when paused at ambient temperature for up to 144 hours. Without atmospheric control, addition of the buffering agent HEPES (25mM) to cell medium was required to keep viability above 70%, as well as to maintain yield and continual passage following 144 hours pausing. The pausing potential of therapeutically relevant human mesenchymal stem cells (hMSCs) from three individual donors (M2, M3 and M4) was tested by keeping cells in suspension for up to 72 hours. Using standard medium with the addition of 25mM HEPES, average membrane integrity was maintained above 70%. Following pausing for between 24 72 hours, hMSC attachment efficiency, immunophenotype and tri-lineage differentiation capacity (osteogenesis, adipogenesis and chondrogenesis) remained similar to non-paused cells. Apart from a short lag phase on the first passage, hMSC fold growth expansion level was consistent with the control for all three donors over 3 x 6 day passages. The colony forming unit (CFU) efficiency of paused cells was significantly reduced when compared with non-paused M2 and M4 lines, whilst M3 retained a similar CFU efficiency to its non-paused counterpart. On return to normal culture conditions, hMSCs had comparable metabolic activity rates with non-paused cells for up to 9 hours. Stable pH is vital during pausing and additional antioxidants or apoptotic inhibiters may be required to keep average viability well-above the 70% threshold, set by the US Food and Drug Administration. Collectively, results have been encouraging and show potential for the movement towards using ambient temperature preservation as an option for the short-term storage and transport of cells for therapy.
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Tutter, Mariella [Verfasser], and Ernst [Akademischer Betreuer] Wagner. "Challenges and chances of the combination of hyperthermia with mesenchymal stem cell-mediated sodium iodide symporter gene therapy / Mariella Tutter ; Betreuer: Ernst Wagner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1211957543/34.
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Legault-Coutu, Daniel. "Studies on mesenchymal stem cells: In vivo identity, cellular biochemistry and use in gene therapy and tissue engineering." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103509.
Повний текст джерелаАнотація:
In 1868, the French experimental physiologist Goujon demonstrated the transplantability and osteogenic potential of bone marrow. More than a hundred years later, Friedenstein first isolated the cells responsible for this osteogenic capacity and demonstrated the existence of a non-hematopoietic stem cell within bone marrow. Since then, the field of mesenchymal stem cell (MSC) research has generated an incredible amount of data aimed at characterizing these cells and indentifying their true in vivo identity and localization, but also exploring their therapeutic potential in animal models. These studies served as a basis for more than 100 human clinical trials using MSCs in the last decade. However, many questions remain unanswered about MSCs. Current research thus aims at improving our understanding of these intriguing cells in order to better use them therapeutically. Four main themes can be identified in MSC research: 1) Characterization and identification of MSCs subsets, 2) Elucidation of the development origin and in vivo identity of MSCs, 3) Identification of the cellular and molecular mechanisms underlying the therapeutic effects of MSCs, and 4) pre-clinical (translational) and clinical use of MSCs. In the manuscript-based thesis presented here, I will present three original research articles covering all four of these themes. In chapter 2, I describe the use of novel cell surface markers to identify MSCs in vivo and in vitro. I initially show that FGF-receptors (FGFRs) are developmentally-regulated in both bone tissues and MSCs. Using these markers, I identified different MSCs subsets in bone tissues including perichondrium, periosteum and trabecular bone. Some of these cells appeared as pericytes in periosteum and trabecular marrow, supporting the model of a perichondrial MSC upstream of a pericytic osteo-stromal progenitor. Finally, I found that FGFRs activation leads to self-renewing proliferation of MSCs in vitro by reversibly inhibiting cellular senescence, providing a biological relevance for the expression of these markers. In chapter 3, I present the preliminary biochemical characterization of periostin, a poorly characterized matricellular protein abundantly expressed by MSCs in vitro and in vivo. I identify a post-translational modification in periostin that will undoubtedly help uncover its roles in MSCs (fate decision, proliferation, migration), in hematopoietic support, and in tissue repair. Finally, in chapter 4 I present our efforts to use MSCs in a cell-based gene therapy approach for hemophilia B. I show that the successful transplantation, engraftment, survival, differentiation, self-renewal and protein delivery by MSCs requires complex tissue engineering techniques and hierarchical scaffold design. More specifically, three-dimensional biomaterials scaffolds required optimization at the nano-, micro- and macroscale in order to sustain long term engraftment and protein delivery by MSCs in a murine model of hemophilia B. Taken together, the findings presented here provide significant advances in understanding MSCs, both in their fundamental biology and therapeutic potential.En 1868, le physiologiste expérimental Goujon démontre que la moelle osseuse peut se transplanter et possède des propriétés ostéogéniques. Près de cent ans plus tard, Friedenstein réussi à isoler les cellules de la moelle responsables de ces propriétés et démontre ainsi l'existence d'une cellule souche non-hématopoïétique résidant dans la moelle osseuse. Depuis, la recherche sur les cellules souches mésenchymateuses (CSM) a généré un nombre considérable d'articles évaluant les caractéristiques in vitro de ces cellules, leur expression de marqueurs de surface, essayant de définir leur identité et leur localisation in vivo, mais aussi testant leurs propriétés thérapeutiques chez les animaux. Ces recherches servirent de base à plus de 100 études cliniques chez l'humain enregistrées jusqu'à maintenant, utilisant les CSM pour traiter diverses maladies. Cependant, plusieurs questions restent non résolues concernant ces intrigantes cellules souches. C'est pourquoi la recherche actuelle sur les CSM tente de répondre à ces questions fondamentales, de manière à pouvoir mieux comprendre les CSM et ainsi à mieux les utiliser thérapeutiquement. On note quatre thèmes majeurs dans la recherche sur les CSM actuelle : 1) la caractérisation in vitro des CSM et l'identification de nouveaux marqueurs de surface, 2) la recherche de l'identité in vivo des CSM et de leur niche ou localisation, 3) l'élucidation des mécanismes cellulaires et moléculaires impliqués dans leurs propriétés thérapeutiques, et 4) la recherche préclinique et clinique utilisant les CSM pour traiter des maladies. Dans la thèse par manuscrits présentée ici, je présente trois articles de recherche couvrant l'ensemble de ces quatre thèmes. Au chapitre 2, j'identifie une famille de récepteurs membranaires qui est régulée de façon développementale dans les tissus osseux et dans les CSM : les récepteurs FGF. Je démontre que ces récepteurs peuvent être utilisés pour identifier les CSM dans différents compartiments osseux tels que le perichondrium, le periosteum et l'os trabéculaire, de manière à suggérer l'existence de CSM primitives dans le perichondrium. Nous verrons également comment l'activation des récepteurs FGF sur les CSM permet leur prolifération tout en inhibant leur sénescence, leur permettant ainsi de s'auto-renouveller. Au chapitre 3, je présente la caractérisation biochimique préliminaire de periostin, une protéine matricellulaire peu connue et abondamment produite par les CSM. J'identifie une modification post-traductionnelle sur periostin qui permettra de mieux comprendre ses divers rôles dans la différentiation des CSM, leur capacité de supporter l'hématopoïèse et de participer à la réparation des tissus endommagés. Finalement, au chapitre 4 je présente une étude visant à utiliser les CSM pour la thérapie génique de l'hémophilie B. Je démontre que la survie, la différentiation, l'auto-renouvellement et la production de protéines thérapeutiques par les CSM après transplantation nécessitent l'utilisation de techniques d'ingénierie tissulaire complexes. Plus spécifiquement, j'ai dû optimiser des biomatériaux 3D à l'échelle nano-, micro- et macroscopique pour permettre la survie et la production de protéine à long-terme par les CSM dans des souris hémophiles. En conclusion, les résultats présentés ici représentent plusieurs avancées significatives dans notre compréhension de la biologie fondamentale des CSM mais également de leurs propriétés thérapeutiques.
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Mathieu, Myrielle. "Comparison between therapeutic efficiency of bone marrow derived mononuclear and mesenchymal stem cells in chronic myocardial infarction." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210138.
Повний текст джерелаАнотація:
Background: Stem cell therapy can facilitate cardiac repair after healed myocardial infarction but the optimal cell type remains uncertain.
Aims: To investigate the pathophysiology of heart failure in a canine model of healed myocardial infarction and to compare the efficacy and the safety of autologous bone marrow mononuclear cell (BMNC) transfer and mesenchymal stem cell (MSC) transfer in this model. It was a blind, randomized and placebo control study.
Methods: Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of BMNC, MSC or Placebo (n = 8 per groups). Echocardiography, conductance method, magnetic resonance imaging, serum neurohormones, holter monitoring, macromorphometry, histology and real time quantitative polymerase chain reaction were used to assess cardiac performance, safety and remodelling in healthy animals, before cell transplantation and up to 16 weeks’ follow-up.
Results: The model was characterized by decreased left ventricular end-systolic elastance and ventricular-arterial uncoupling without alteration of compliance.
Four months after BMNC transfer, the regional systolic function measured at echocardiographic showed a sustained improvement. This improvement was associated with an improved left ventricular end-systolic elastance and a decreased infarct size. Although the left ventricular ejection fraction stayed unchanged, the serum level of N-terminal B-type natriuretic propeptide level decreased. Mononuclear cell transfer was also associated with increased left ventricular relative wall area, increased vascular density, intramyocardial vascular remodelling and upregulation of angiogenic factors gene expression. Mesenchymal stem cell transfer only improved lately and moderately the regional systolic function, without improvement of cardiac contractility or decreased infarct size.
Conclusions: In a canine model of chronic myocardial infarction, BMNC transfer is superior to MSC transfer in improvement of cardiac contractility and regional systolic function, and to reduce the infarct size and plasma N-terminal B-type natriuretic propeptide level. Functional improvement is associated with a favourable angiogenic environment and neovascularization.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
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Hagenhoff, Anna Maria [Verfasser], and Peter [Akademischer Betreuer] Nelson. "Engineered mesenchymal stem cells In tumor therapy : a comparison of three targeting strategies / Anna Maria Hagenhoff ; Betreuer: Peter Nelson." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1163200905/34.
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Knoop, Kerstin [Verfasser], and Ernst [Akademischer Betreuer] Wagner. "Molecular imaging and radionuclide therapy in non-thyroidal tumors after mesenchymal stem cell- mediated sodium/iodide symporter (NIS) gene transfer / Kerstin Knoop. Betreuer: Ernst Wagner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1065180403/34.
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Thieme, Sebastian, Sabine Stopp, Martin Bornhäuser, Fernando Ugarte, Manja Wobus, Matthias Kuhn, and Sebastian Brenner. "Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-178636.
Повний текст джерелаАнотація:
The melanoma cell adhesion molecule defines mesenchymal stromal cells in the human bone marrow that regenerate bone and establish a hematopoietic microenvironment in vivo. The role of the melanoma cell adhesion molecule in primary human mesenchymal stromal cells and the maintenance of hematopoietic stem and progenitor cells during ex vivo culture has not yet been demonstrated. We applied RNA interference or ectopic overexpression of the melanoma cell adhesion molecule in human mesenchymal stromal cells to evaluate the effect of the melanoma cell adhesion molecule on their proliferation and differentiation as well as its influence on co-cultivated hematopoietic stem and progenitor cells. Knockdown and overexpression of the melanoma cell adhesion molecule affected several characteristics of human mesenchymal stromal cells related to osteogenic differentiation, proliferation, and migration. Furthermore, knockdown of the melanoma cell adhesion molecule in human mesenchymal stromal cells stimulated the proliferation of hematopoietic stem and progenitor cells, and strongly reduced the formation of long-term culture-initiating cells. In contrast, melanoma cell adhesion molecule-overexpressing human mesenchymal stromal cells provided a supportive microenvironment for hematopoietic stem and progenitor cells. Expression of the melanoma cell adhesion molecule increased the adhesion of hematopoietic stem and progenitor cells to human mesenchymal stromal cells and their migration beneath the monolayer of human mesenchymal stromal cells. Our results demonstrate that the expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells determines their fate and regulates the maintenance of hematopoietic stem and progenitor cells through direct cell-cell contact.
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Thieme, Sebastian, Sabine Stopp, Martin Bornhäuser, Fernando Ugarte, Manja Wobus, Matthias Kuhn, and Sebastian Brenner. "Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells." Ferrata Storti Foundation, 2013. https://tud.qucosa.de/id/qucosa%3A28908.
Повний текст джерелаАнотація:
The melanoma cell adhesion molecule defines mesenchymal stromal cells in the human bone marrow that regenerate bone and establish a hematopoietic microenvironment in vivo. The role of the melanoma cell adhesion molecule in primary human mesenchymal stromal cells and the maintenance of hematopoietic stem and progenitor cells during ex vivo culture has not yet been demonstrated. We applied RNA interference or ectopic overexpression of the melanoma cell adhesion molecule in human mesenchymal stromal cells to evaluate the effect of the melanoma cell adhesion molecule on their proliferation and differentiation as well as its influence on co-cultivated hematopoietic stem and progenitor cells. Knockdown and overexpression of the melanoma cell adhesion molecule affected several characteristics of human mesenchymal stromal cells related to osteogenic differentiation, proliferation, and migration. Furthermore, knockdown of the melanoma cell adhesion molecule in human mesenchymal stromal cells stimulated the proliferation of hematopoietic stem and progenitor cells, and strongly reduced the formation of long-term culture-initiating cells. In contrast, melanoma cell adhesion molecule-overexpressing human mesenchymal stromal cells provided a supportive microenvironment for hematopoietic stem and progenitor cells. Expression of the melanoma cell adhesion molecule increased the adhesion of hematopoietic stem and progenitor cells to human mesenchymal stromal cells and their migration beneath the monolayer of human mesenchymal stromal cells. Our results demonstrate that the expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells determines their fate and regulates the maintenance of hematopoietic stem and progenitor cells through direct cell-cell contact.
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Sun, Jianan. "Protective Effects of Human iPS-Derived Retinal Pigmented Epithelial Cells in Comparison with Human Mesenchymal Stromal Cells and Human Neural Stem Cells on the Degenerating Retina in rd1 Mice." Kyoto University, 2016. http://hdl.handle.net/2433/215387.
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Schneider, Fabrice. "Remodelage de la paroi artérielle : étude des aspects de destruction et de reconstruction." Thesis, Paris Est, 2011. http://www.theses.fr/2011PEST0101/document.
Повний текст джерелаАнотація:
L’athérosclérose et la pathologie anévrysmale sont principalement caractérisées par un remodelage de laparoi artérielle au cours de leur évolution. Ce travail a examiné un aspect de la destruction de la paroiartérielle à travers l’étude de la métalloprotéase MMP-14 au cours de l’athérome et un aspect dereconstruction artérielle à travers l’étude d’une thérapie cellulaire d’un modèle d’Anévrysme de l’AorteAbdominale (AAA) par Cellules Souches Mésenchymateuses (CSMs).En utilisant un modèle de greffe de Moëlle Osseuse (MO) dans des souris Ldlr-/-, nous avons montré que ladélétion d’expression de MMP-14 dans les cellules issues de la MO provoquait une accumulation decollagène interstitiel dans la plaque athéromateuse sans modification de la composition cellulaire nivariation de taille. Une mesure de l’activité collagénolytique par substrat fluorescent a confirmé que ladélétion en MMP-14 chez les macrophages provoquait une baisse de l’activité collagénolytique. Cetteactivité est indépendante de l’activité MMP-2 et MMP-8 et pourrait être médiée partiellement parl’activation de MMP-13. Nous avons mis en évidence la présence de CSMs à la surface luminale de thrombus de AAA et nous avonsmontré une diminution significative des CSMs circulantes chez des patients porteurs de AAA. Nous avonspu stabiliser la croissance de AAA expérimentaux chez le rat à partir de xénogreffe artérielle par perfusionendoluminale de CSMs. La perfusion de CSMs provoquait une diminution de l’inflammation à court termeet favorisait la reconstruction artérielle par accumulation de collagène et d’élastine à moyen terme.En conclusion, l’activité collagénolytique de MMP-14 est un des mécanismes moléculaires possibles del’évolution de la plaque athéromateuse par rupture de plaque. Elle ouvre la perspective d’une nouvelleapproche thérapeutique et pourrait être une cible comme substrat pour une imagerie fonctionnelle de laplaque athéromateuse. L’évolution de la maladie anévrysmale pourrait être secondaire à une altération dessystèmes de réparation tissulaire dont les CSMs seraient des acteurs clé. La perfusion endoluminale desCSMs dans un modèle expérimental a permis la restauration de ces systèmes de réparation tissulaire etouvre la perspective d’un nouvel outil thérapeutique contre les AAAPas de résumé anglais
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Valim, Vanessa de Souza. "Estudo sobre condições do cultivo de células-tronco mesenquimais para aplicações clínicas." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/61272.
Повний текст джерелаАнотація:
Introdução: Células-troco mesenquimais (CTM) vêm mostrando seus benefícios na doença do enxerto-versus-hospedeiro (DECH), observada no transplante de células tronco hematopoéticas (TCTH), existem três questões em aberto: (1) Expansão de CTM em meio de cultura suplementado com soro fetal bovino (SFB), pelo o risco de xenorreação; (2) Otimização de condições de cultura para a obtenção, em tempo hábil, de um numero que permita de 4 a 6 infusões de 2x106cells/kg do receptor; (3) Obter células do doador de medula óssea, evitando assim a utilização de um terceiro doador. Objetivos: Este estudo foi desenhado para comparar o lisado de plaquetas (LP) e o SFB na expansão de CTM, a densidade de plaqueamento das células e os dias entre cada passagem, e para investigar se as células nucleadas totais obtidas da bolsa e filtro do TCTH, podem ser utilizadas para expansão de CTM para utilização clínica. Métodos: Células residuais foram removidas do filtro e da bolsa utilizados para o TCTH, plaqueadas e depois da primeira passagem foram cultivadas em diferentes concentrações com SFB ou LP e observado o número de dias que levaram para chegar a 80% de confluência. Em seguida, as culturas com as mesmas densidades de plaqueamento foram suplementadas com LP ou SFB e depois de sete dias contou-se o número de células para analisar o quanto elas cresceram nesse período. Resultados: A proliferação de CTM, na presença de LP e SFB foi em média 11,88 e 2,5 vezes, respectivamente, num período de 7 dias. A concentração mais elevada de células usando LP demorou menos tempo para atingir a confluência, em comparação com os três inferiores. Este estudo sugere que o LP é a melhor escolha como suplemento para expandir CTM, e permite a proliferação de um número suficiente de CTM de doadores para uso clínico.Introduction: Mesenchymal stromal cells (MSC) have shown their benefits in graft-versus-host disease (GVHD), with three unsettled matters:(1) MSCs expansion in medium with Fetal Calf Serum (FCS) and its risk of xenoreaction; (2) The number of cells indicated for therapy is 2x106cells/Kg with the need to optimize expansion, number and time wise; and (3) the utilization of third party donors. Aims: This study was designed to compare the platelet lysate (LP) and FCS on the expansion of MSC, the optimal cell plating density and days between each pass, and to investigate if donor total nucleated cells (TNC) obtained from the washouts of hematopoietic stem cell transplantation (HSCT) explants can be expanded to be used at clinical grade. Methods: TNC were removed, plated and after the first passage were cultivated in different concentrations with FCS or PL and the number of days reach 80% of confluence was observed. Next, cultures with the same plating density were fed either with PL or FCS and after seven days counted to analyze how much they have grown in that period. Results: The proliferation of mesenchymal stromal cells in the presence of PL and SFB was averaged 11.88 and 2.5 times, respectively, in a period of 7 days. The highest concentration of plating cells using PL, took less time to reach confluence as compared with the three lower ones. This study suggests that the PL is the best choice as a supplement to expand MSC, and allows the proliferation of a sufficient number of donors MSC at P2 for clinical use.
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Kucic, Terrence. "Exploiting the use of mesenchymal stromal cells genetically engineered to overexpress insulin-like growth factor-1 in gene therapy of chronic renal failure." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112527.
Повний текст джерелаАнотація:
Mesenchymal stromal cells (MSC) are bone marrow-derived, non-hematopoietic progenitors that are amenable to genetic engineering, making them attractive delivery vehicles for therapeutic proteins. However, limited transplanted cell survival compromises the efficacy of MSC-based gene therapy. We hypothesized that co-implantation of insulin-like growth factor-1 (IGF-I)-overexpressing MSC (MSC-IGF) would improve MSC-based therapy of anemia by providing paracrine support to erythropoietin (EPO)-secreting MSC (MSC-EPO). Murine MSC were found to express the IGF-I receptor and be responsive to IGF-I stimulation. IGF-I also improved MSC survival in vitro. MSC were admixed in a bovine collagen matrix and implanted by subcutaneous injection in a murine model of chronic renal failure. Mice receiving MSC-EPO co-implanted with MSC-IGF experienced a greater and significantly sustained elevation in hematocrit compared to controls; heart function was also improved. Co-implantation of MSC-IGF therefore represents a promising new strategy for enhancing implanted cell survival, and improving cell-based gene therapy of renal anemia.
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Bach, Martin. "Der Einfluss muriner mesenchymaler Stammzellen auf murine zytokin induzierte Killerzellen in der Kokultur." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-149957.
Повний текст джерелаАнотація:
Stimulating lymphocytes with Ifn-γ, anti-CD3, and interleukin-2 promotes the proliferation of a cell population coexpressing T-lymphocyte surface antigens such as CD3, CD8a, and CD25 as well as natural killer cell markers such as NK1.1, CD49, and CD69. These cells, referred to as cytokine-induced killer cells (CIKs), display cytotoxic activity against tumour cells, even without prior antigen presentation, and offer a new cell-based approach to the treatment of malignant diseases. Because CIKs are limited in vivo, strategies to optimize in vitro culture yield are required.
In the last 10 years, mesenchymal stem cells (MSCs) have gathered considerable attention. Aside from their uses in tissue engineering and as support in haematopoietic stem cell transplantations, MSCs show notable immunomodulatory characteristics, providing further possibilities for therapeutic applications. In this study, we investigated the influence of murine MSCs on proliferation, phenotype, vitality, and cytotoxicity of murine CIKs in a coculture system. We found that CIKs in coculture proliferated within 7 days, with an average growth factor of 18.84, whereas controls grew with an average factor of 3.7 in the same period. Furthermore, higher vitality was noted in cocultured CIKs than in controls. Cell phenotype was unaffected by coculture with MSCs and, notably, coculture did not impact cytotoxicity against the tumour cells analysed. The findings suggest that cell–cell contact is primarily responsible for these effects. Humoral interactions play only a minor role. Furthermore, no phenotypical MSCs were detected after coculture for 4 h, suggesting the occurrence of immune reactions between CIKs and MSCs. Further investigations with DiD-labelled MSCs revealed that the observed disappearance of MSCs appears not to be due to differentiation processes.