Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and debilitating adverse complication of cancer treatment due to damage to peripheral dorsal root ganglion sensory neurons. While neuronal toxicity has been well-established and extensively explored, the contribution of satellite glial cells, non-neuronal cells that ensheath sensory neuron somata in vivo, remains under-explored. The aim of this thesis was to investigate the role of satellite glia in contributing to neuronal susceptibility to chemotherapeutic toxicity and to develop advanced applications for new avenues to explore neuron-glial interactions relevant to human peripheral neuropathy pathogenesis. We observed that induced pluripotent stem cells (iPSC)-derived sensory neurons terminally differentiated in coculture with rat dorsal root ganglion satellite glial cells exhibited increased susceptibility to paclitaxel-induced degeneration compared to those terminally differentiated alone. Additionally, we established methods for expanding, cryopreserving, and replating rat satellite glial cells, demonstrating these cells can be maintained and banked while retaining a satellite glial phenotype and function. These cells were further integrated into coculture systems for advanced peripheral neuropathy modeling. Finally, we explored new differentiation approaches to generate satellite glial cells from iPSC-derived human glial precursor populations by leveraging developmental cues. Together, this work highlights the importance of satellite glial cells in shaping neuronal responses to chemotherapy-induced degeneration, establishes novel experimental models investigating satellite glial contributions to human peripheral neuropathies, and explores complex pathways underlying glial development.