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dc.contributor.advisorKrystyn J. Van Vliet and Daniel G. Anderson.en_US
dc.contributor.authorEspinosa-Hoyos, Daniela.en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Chemical Engineering.en_US
dc.date.accessioned2021-01-06T19:34:20Z
dc.date.available2021-01-06T19:34:20Z
dc.date.copyright2020en_US
dc.date.issued2020en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/129235
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, September, 2020en_US
dc.descriptionCataloged from student-submitted PDF of thesis.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractThe brain is the powerhouse of the central nervous system (CNS). When this system is out of balance, the implications are massive: neurological diseases are the leading cause of disability and number two leading cause of fatalities in the world. Returning the system to its steady state parallels in complexity. Despite the challenges in drug discovery and development for CNS disorders that have contributed to the shut-down of entire neuroscience programs in the pharmaceutical industry, the massive unmet need continues to motivate basic research and innovation in this space: there are no cures for CNS disorders. Myelin and oligodendroglia--the myelinating cells of the CNS--play central roles in homeostasis, and the pathogenesis of a myriad of neurological disorders, including multiple sclerosis. Academic and industrial researchers need new tools, which include new materials and procedures, to develop new strategies for myelin and oligodendroglial protection and repair.en_US
dc.description.abstractThis thesis leverages interdisciplinary technologies and concepts to address challenges and inefficiencies in the current approach to discover and develop therapies for myelin disorders. We sought to address the need for preclinical in vitro tools compatible with high content screening that can replicate key aspects of myelination and the oligodendroglial niche. Inspired by physical and mechanical properties of neuronal axons, we developed new compliant and biocompatible polymers and additive manufacturing methodology to create Artificial Axons. We established primary rat myelination assays and showed that Artificial Axons capture key properties of oligodendroglial and neuronal interactions, which can be imaged in real time, and quantified.en_US
dc.description.abstractWe implemented induced pluripotent stem cell technology to demonstrate that some but not all aspects of oligodendrocyte mechanotransduction are conserved across rats and humans in vitro, further motivating the use of human cells for the study of uniquely human diseases. We also demonstrated the first quantitative axon-free human myelination assays, and explored their use in drug discovery, including for dose response and small molecule screening. Finally, we discuss the modification of these assays and manufacturing methodologies, including harnessing material properties, to scale up the fabrication of Artificial Axons with better spatial resolution for high content screening.en_US
dc.description.statementofresponsibilityby Daniela Espinosa-Hoyos.en_US
dc.format.extent436 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemical Engineering.en_US
dc.titleEngineering myelination in vitroen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.identifier.oclc1227513784en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Department of Chemical Engineeringen_US
dspace.imported2021-01-06T19:34:19Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentChemEngen_US


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