VCOM Research Day Program Book 2023

Medical Student Research Biomedical

23 Peripheral Nerve Regeneration: The Implications of Schwann Cells with Neuronal Small Vesicles

Zachary T. Simmons; Valerie Zanin; Kelly C.S. Roballo Corresponding author: zsimmons@vt.vcom.edu

Edward Via College Of Osteopathic Medicine-Virginia Campus

Peripheral nerves (PN’s) are frequently injured from trauma and disease. The regeneration capacity of the PNs varies depending on the extent of injury and complications that may arise with Wallerian degeneration. Despite recent advancements in PN transplant, many patients still experience suboptimal outcomes due to the intricacies of axonal regeneration. With the potential to increase the likelihood of optimal outcomes, we investigate the capability of small vesicles (formerly known as exosomes) to induce neuronal differentiation and regeneration. This project capitalizes on that aspect and is specific to the use of Schwann Cells (SC’s), which coat and support the neuron in the periphery, and the small vesicles of neurons themselves. In more detail, we have investigated mechanisms to utilize small vesicle regenerative capability by exploring how different concentrations and conditions affect neuronal exosome uptake by the SC’s. Further, we have postulated that priming the exosomes through

co-culture with varying peripheral nerve cell types will increase the exosome’s tendency for uptake and long-term cell survival; thus minimizing the likelihood of axonal degeneration. In this project we isolated neuron-derived small vesicles and SC-derived small vesicles, and we co-cultured these vesicles with SCs over 24hrs (priming or previous exposure). After 24hr co-cultures, these vesicles were once again isolated and cultured with SCs. The idea was to evaluate if the SCs neuron-derived small vesicle uptake would increase after priming these vesicles. Overall, our data demonstrated that SCs are able to receive primed neuron-derived small vesicles and primed SC derived small vesicles up to seven days, and more time exposed to primed neuron-derived small vesicles led to more uptake. The concentration of 25ul/ml of primed SC-derived small vesicle demonstrated better uptake by SCs than 10ul/mL, and both 10 and 25ul/mL of primed neuron-derived small vesicle were proportionally taken up by SCs. Our

findings suggest that primed small vesicles increase the uptake of exosomes by the SC which could serve as a therapeutic benefit to peripheral nerve transplant and regeneration. Ultimately, we also hope to explore drug delivery capabilities of peripheral nerve cell exosomes and improve the outcome of peripheral nerve damage.

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