Immunoengineering Trainee Seminar

 

 

How can we determine whether neural extracellular vesicles (EVs) retain biological activity after changes in manufacturing or storage? This project evaluates microglial morphology as a quantitative readout of recipient-cell responses to neural stem cell-derived EV preparations. Using isolation and storage methods as a case study, this novel microglial morphology assay connects physical characterization of EVs with image-based measurements of cell and nuclear morphology. The results reveal a dose-dependent morphology response, with no significant differences detected between cryopreserved and lyophilized preparations at matched doses under the tested conditions. We will explore how this assay could support EV development, what morphology can tell us about immune-cell behavior, and which complementary functional measurements could strengthen its use as an immunoengineering platform.

 

Aging progressively impairs CD8+ T cell activation, proliferation, and cytotoxic function, contributing to weakened immune responses against infections and cancer. MicroRNAs (miRNAs) regulate key transcriptional and signaling pathways involved in T cell function, offering a promising strategy to reverse age-associated dysfunction. However, efficient delivery of miRNAs into resting aged T cells remains a major technical challenge.

 

In this talk, I will present a biomaterial-based silicon nanowire platform that enables efficient, non-viral delivery of miRNAs into aged CD8+ T cells with over 90% delivery efficiency while maintaining high cell viability. By modulating individual miRNAs, we demonstrate that T cell activation and differentiation can be directed toward distinct functional states. Building on these findings, we developed a multiplexed miRNA delivery strategy that simultaneously targets complementary regulatory pathways, enhancing T cell activation, effector differentiation, cytokine production, and cytotoxic molecule expression. Importantly, multiplexed miRNA delivery also improves metabolic activity and proliferative capacity in aged T cells. We further demonstrate consistent enhancement of activation and cytotoxic responses in primary human CD8+ T cells from healthy older individuals, lymphoma survivors, and patients with solid tumors. Initial in vivo studies additionally suggest improved early effector priming following influenza infection.

 

Together, this work highlights the potential of biomaterial-enabled intracellular programming to restore functional responses in aged immune cells and provides a foundation for future strategies to improve immune function in older populations.