Myelination and node of Ranvier formation play an important role in saltatory conduction of axonal action potentials in the peripheral nervous system (PNS). Degeneration or damage of this myelin can lead to impairment in the conduction of signals by the axons, and cause deficits in sensory and motor function. Currently, animal-based models are the primary method used to study myelination; however, data generated in animal models generally translate poorly to humans, especially as applied to drug discovery. In order to accurately study myelination in humans without having to rely on human testing, an engineered in vitro model of myelination could go a long way in helping us understand the mechanisms of myelination, as well as provide a platform to test drugs or therapeutics to treat diseases that affect myelination. Here we report the complete development and characterization of the first human myelination model using human primary Schwann cells (SCs) and human iPSC-derived motoneurons (iPSC-MNs) as well as some data collected from furthering this work utilizing iPSC derived Schwann cells. Myelination and node of Ranvier formation in co-cultured iPSC human motoneurons and primary human SCs were characterized via flow cytometry, immunocytochemistry, and 3D confocal Raman microscopy, and furthering of this work using iPSC derived human Schwann cells characterized using immunocytochemistry is also presented. This novel human-based myelination model will be a more accurate tool when it comes to the study of myelination and demyelinating diseases in humans, as well as elucidation of mechanisms of myelination. This system(s) could be used to determine efficacy of novel therapeutics for demyelinating diseases such as Charcot-Marie Tooth, Guillian-Barre syndrome, anti-MAG peripheral neuropathy, as well as the testing of treatments for the regeneration of damaged peripheral myelination from other causes.
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Master of Science (M.S.)
College of Graduate Studies
Nanoscience Technology Center
Length of Campus-only Access
Masters Thesis (Open Access)
Patel, Aakash, "Development and Characterization of a Novel Serum Free Human iPSC Motoneuron-Primary Human Schwann Cell Model of Myelination" (2020). Electronic Theses and Dissertations, 2020-. 615.