Дисертації з теми "Engineered Heart Muscle Tissues"
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Fernández, Garibay Xiomara Gislen. "Engineered functional skeletal muscle tissues for in vitro studies." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/673232.
Повний текст джерелаEl músculo esquelético tiene funciones esenciales para la salud que pueden verse afectadas por enfermedades neuromusculares o metabólicas. Actualmente, la investigación fundamental y preclínica se basa en cultivos celulares en 2D y modelos animales. Sin embargo, estos ensayos tienen relevancia limitada para la salud humana. En cambio, modelos in vitro de tejidos 3D que mimeticen la arquitectura y funcionalidad del músculo esquelético, podrían complementar las estrategias 2D tradicionales. Por lo tanto, el objetivo principal de esta tesis fue desarrollar tejidos de músculo esquelético en 3D para estudios sobre el metabolismo muscular y modelos de enfermedades in vitro. Los tejidos fueron desarrollados mediante diferentes técnicas de microfabricación de hidrogeles, en los que se encapsularon células precursoras del músculo esquelético introduciendo las señales topográficas adecuadas para guiar la formación de fibras musculares. Las propiedades de estos biomateriales fueron optimizadas para garantizar su biocompatibilidad y promover la miogénesis. Estos biomateriales mantienen su estructura durante periodos de cultivo prolongados, permitiendo la formación y diferenciación de miotubos 3D altamente alineados. La función endócrina de los tejidos fue evaluada utilizando un dispositivo músculo-en-un-chip, con el que fue posible medir la liberación de citoquinas secretadas tras estimulación eléctrica o biológica. Posteriormente, se desarrolló el primer modelo 3D de músculo esquelético humano para la distrofia miotónica tipo 1. Como prueba de concepto, demostramos que el tratamiento con un oligonucleótido antisentido, antagomiR-23b, podría rescatar fenotipos moleculares y estructurales en los tejidos fabricados a partir de células de pacientes. Finalmente, se desarrollaron tejidos funcionales en cultivos celulares xeno-free, con el objetivo de incrementar la relevancia de modelos humanos en los que fue posible medir las fuerzas generada por tejidos contráctiles. En conjunto, los resultados de esta tesis proporcionan enfoques prometedores para modelos avanzados de músculo esquelético que podrían ser herramientas valiosas para estudios fundamentales, modelos de enfermedades y medicina personalizada.
Kim, Hyeon Yu Ph D. Massachusetts Institute of Technology. "Enhancing functionalities of engineered skeletal muscle tissues by recreating natural environmental cues." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122138.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (pages 101-112).
Engineered skeletal muscle tissue is a three-dimensional contractile tissue made from muscle cells and the extracellular matrix (ECM). It can be used as a drug testing platform or an implantable tissue, but its practical use has been limited by inferior contractile performance and small size compared to natural muscles. This thesis aims to implement environmental cues and essential elements of natural muscles to improve the contractile performance and increase its size beyond the diffusion limit. Firstly, inspired by the observation that the natural muscles are exposed to electric potentials from neurons in combination with mechanical stretching from surrounding muscles, a new muscle training system was developed to apply coordinated electrical and mechanical stimulation.
Both the experimental results and the mechanistic model suggest the combined stimulation reorients the ECM fibers in such a way that the parallel ECM stiffness is reduced, while the serial ECM stiffness is increased, which reduces resistance to muscle contraction and increases force transmission in the engineered muscles, respectively. Secondly, large-sized natural muscles are fully vascularized so that oxygen and nutrients can be supplied. However, vascularization of the engineered skeletal muscle has been challenging because the microenvironmental requirement for differentiating myoblasts is incompatible with the one for culturing endothelial cells. In contrast, the natural muscle tissue has a compartment structure, where endothelial cells are exposed to blood plasma, while myoblasts are surrounded by interstitial fluid.
In this thesis, we modeled the natural fluid compartments by creating an in vitro perfusable vasculature running through a skeletal muscle tissue with physiologic cell density. The tissue is designed to have a coaxial tubular shape with a perfusable vasculature at the center. Through the in vitro fluid compartments, endothelial cells are exposed to endothelial cell growth medium running through the vascular channel, and the skeletal muscle cells are surrounded by muscle differentiation medium. By using this platform, engineered muscle tissue was successfully scaled up from microscale to subcentimeter scale. This platform also enabled to show that coculturing with the two separate media from an early stage of muscle differentiation leads to increased contractile force, thicker myotubes, and more muscle differentiation compared to using a single coculture medium.
Furthermore, the engineered skeletal muscles were further vascularized by inducing angiogenic sprouting from the vascular channel penetrating into the muscle tissue. This thesis will contribute to utilizing engineered skeletal muscles in practical applications with improved functionalities and provide a new model to study heterotypic cell-cell interactions in skeletal muscle tissues.
by Hyeon Yu Kim.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Mechanical Engineering
Ciucci, Giulio. "Engineered heart tissues to investigate the role of mechanical loading and injury in cardiomyocyte proliferation." Doctoral thesis, Università degli studi di Trento, 2021. http://hdl.handle.net/11572/312213.
Повний текст джерелаGreer, Linda S. "Material property testing of a collagen/smooth muscle cell gel for the development of a tissue engineered vascular graft." Thesis, Georgia Institute of Technology, 1994. http://hdl.handle.net/1853/33447.
Повний текст джерелаLetuffe-Brenière, David [Verfasser], and Thomas [Akademischer Betreuer] Eschenhagen. "Modelling catecholaminergic polymorphic ventricular tachycardia with patient-specific iPSC-derived engineered heart tissues / David Letuffe-Brenière. Betreuer: Thomas Eschenhagen." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://d-nb.info/1095766554/34.
Повний текст джерелаLetuffe-Brenière, David Verfasser], and Thomas [Akademischer Betreuer] [Eschenhagen. "Modelling catecholaminergic polymorphic ventricular tachycardia with patient-specific iPSC-derived engineered heart tissues / David Letuffe-Brenière. Betreuer: Thomas Eschenhagen." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://nbn-resolving.de/urn:nbn:de:gbv:18-77988.
Повний текст джерелаLevent, Elif [Verfasser], Wolfram-Hubertus [Akademischer Betreuer] Zimmermann, Dörthe [Gutachter] Katschinski, and Susanne [Gutachter] Lutz. "Characterization of cardiac progenitor cell activity in engineered heart muscle / Elif Levent. Betreuer: Wolfram-Hubertus Zimmermann. Gutachter: Dörthe Katschinski ; Susanne Lutz." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2016. http://d-nb.info/1104480476/34.
Повний текст джерелаGolat, Brian [Verfasser], Wolfram-H. [Akademischer Betreuer] Zimmermann, Rüdiger [Gutachter] Behr, Lutz [Gutachter] Walter, Ralf [Gutachter] Dressel, Stefan [Gutachter] Luther, and Steven [Gutachter] Johnsen. "Development of a Rhesus macaque engineered heart muscle model from pluripotent stem cells / Brian Golat ; Gutachter: Rüdiger Behr, Lutz Walter, Ralf Dressel, Stefan Luther, Steven Johnsen ; Betreuer: Wolfram-H. Zimmermann." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2017. http://d-nb.info/1135487715/34.
Повний текст джерелаGolat, Brian. "Development of a Rhesus macaque engineered heart muscle model from pluripotent stem cells." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-0023-3E73-D.
Повний текст джерелаSchlick, Susanne. "Fibroblast-Cardiomyocyte Cross-Talk in Heart Muscle Formation and Function." Doctoral thesis, 2018. http://hdl.handle.net/11858/00-1735-0000-002E-E57D-3.
Повний текст джерелаSoong, Poh Loong. "Development of a novel technology to engineer heart muscle for contractile and paracrine support in heart failure." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-F03B-7.
Повний текст джерелаLevent, Elif. "Characterization of cardiac progenitor cell activity in engineered heart muscle." Doctoral thesis, 2016. http://hdl.handle.net/11858/00-1735-0000-0028-8791-C.
Повний текст джерелаBaltzer, Anne. "Über die Auswirkung mechanische Last auf die Entwicklung von künstlichem Herzgewebe." Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0023-9948-B.
Повний текст джерелаNoblet, Jillian Nicole. "Coronary perivascular adipose tissue and vascular smooth muscle function: influence of obesity." Diss., 2016. http://hdl.handle.net/1805/9815.
Повний текст джерелаFactors released from coronary perivascular adipose tissue (PVAT), which surrounds large coronary arteries, have been implicated in the development of coronary disease. However, the precise contribution of coronary PVAT-derived factors to the initiation and progression of coronary vascular dysfunction remains ill defined. Accordingly, this investigation was designed to delineate the mechanisms by which PVAT-derived factors influence obesity-induced coronary smooth muscle dysfunction. Isometric tension studies of coronary arteries from lean and obese swine demonstrated that both lean and obese coronary PVAT attenuate vasodilation via inhibitory effects on smooth muscle K+ channels. Specifically, lean coronary PVAT attenuated KCa and KV7 channel-mediated dilation, whereas obese coronary PVAT impaired KATP channel-mediated dilation. Importantly, these effects were independent of alterations in underlying smooth muscle function in obese arteries. The PVAT-derived factor calpastatin impaired adenosine dilation in lean but not obese arteries, suggesting that alterations in specific factors may contribute to the development of smooth muscle dysfunction. Further studies tested the hypothesis that leptin, which is expressed in coronary PVAT and is upregulated in obesity, acts as an upstream mediator of coronary smooth muscle dysfunction. Long-term administration (3 day culture) of obese concentrations of leptin markedly altered the coronary artery proteome, favoring pathways associated with calcium signaling and cellular proliferation. Isometric tension studies demonstrated that short-term (30 min) exposure to leptin potentiated depolarization-induced contraction of coronary arteries and that this effect was augmented following longer-term leptin administration (3 days). Inhibition of Rho kinase reduced leptin-mediated increases in coronary artery contractions. Acute treatment was associated with increased Rho kinase activity, whereas longer-term exposure was associated with increases in Rho kinase protein abundance. Alterations in Rho kinase signaling were also associated with leptin-mediated increases in coronary vascular smooth muscle proliferation. These findings provide novel mechanistic evidence linking coronary PVAT with vascular dysfunction and further support a role for coronary PVAT in the pathogenesis of coronary disease.
Owen, Meredith Kohr. "Effect of coronary perivascular adipose tissue on vascular smooth muscle function in metabolic syndrome." Thesis, 2013. http://hdl.handle.net/1805/3789.
Повний текст джерелаObesity increases cardiovascular disease risk and is associated with factors of the “metabolic syndrome” (MetS), a disorder including hypertension, hypercholesterolemia and/or impaired glucose tolerance. Expanding adipose and subsequent inflammation is implicated in vascular dysfunction in MetS. Perivascular adipose tissue (PVAT) surrounds virtually every artery and is capable of releasing factors that influence vascular reactivity, but the effects of PVAT in the coronary circulation are unknown. Accordingly, the goal of this investigation was to delineate mechanisms by which lean vs. MetS coronary PVAT influences vasomotor tone and the coronary PVAT proteome. We tested the hypothesis that MetS alters the functional expression and vascular contractile effects of coronary PVAT in an Ossabaw swine model of the MetS. Utilizing isometric tension measurements of coronary arteries in the absence and presence of PVAT, we revealed the vascular effects of PVAT vary according to anatomical location as coronary and mesenteric, but not subcutaneous adipose tissue augmented coronary artery contractions to KCl. Factors released from coronary PVAT increase baseline tension and potentiate constriction of isolated coronary arteries relative to the amount of adipose tissue present. The effects of coronary PVAT are elevated in the setting of MetS and occur independent of endothelial function. MetS is also associated with substantial alterations in the coronary PVAT proteome and underlying increases in vascular smooth muscle Ca2+ handling via CaV1.2 channels, H2O2-sensitive K+ channels and/or upstream mediators of these ion channels. Rho-kinase signaling participates in the increase in coronary artery contractions to PVAT in lean, but not MetS swine. These data provide novel evidence that the vascular effects of PVAT vary according to anatomic location and are influenced by the MetS phenotype.