S'Dravious DeVeaux
BME PhD Defense Presentation
Date: 2024-09-09
Time: 9:00-11:00 AM
Location / Meeting Link: EBB CHOA / https://gatech.zoom.us/j/98604729108
Committee Members:
Edward Botchwey, PhD (Advisor); Krishnendu Roy, PhD (Co-Advisor); Aditi Das, PhD; Carolyn Yeago, PhD; Facundo Fernandez, PhD; Melissa Kemp, PhD
Title: Assessing Potency of Mesenchymal Stromal Cells by Lipid Profiling of Sphingolipids
Abstract:
The cell therapeutic industry is expected to significantly grow over the next few decades and is projected to be worth $11 billion USD by 2030. With the expected growth of cell therapies, scaling methods, standardized process parameters, and cell manufacturing strategies are being expanded to meet clinical demand. Mesenchymal stromal cells (MSCs) have gained traction as a potential cell therapy due to their multipotent differentiation capacity, immunomodulation, and tissue regenerative capabilities via paracrine signaling. Despite their therapeutic potential, discrepancies in MSC characterization have limited further clinical application. Currently, the minimal criteria for MSC characterization are adherence to plastic, expression of specific surface antigens, and multipotent differential potential in vitro, however the International Society of Cell & Gene Therapy has more recently called for improvements to MSC characterization, suggesting omic characterization with functional tests to better explain MSCs’ potency. Lipidomics, a sub-branch of metabolomics, is a powerful technique that combines high-throughput analytical methods and informatics to quantify and characterize lipids in a biological system. This technique can be used for cell characterization as it provides a scope of a cell’s entire lipid profile to understand their role in complex cell signaling. Sphingolipids (SLs) are a class of bioactive lipids that participate in signaling processes involving proliferation, cell differentiation, immune cell trafficking, and extracellular vesicle (EV) biogenesis. However, their role in MSC behavior and potency remains largely unknown. This work aims to understand how bioactive SLs are involved in MSC therapeutic properties. In Aim 1, liquid chromatography-tandem mass spectrometry was utilized to target and characterize MSCs SL profile from multiple tissue sources and after stimulation with a pro-inflammatory cytokine. In Aim 2, MSC SL metabolic network was modulated by an exogenous SL enzyme. We conducted multi-omic characterization after enzyme treatment on MSCs and their EVs. The findings of this work can help develop an understanding of SL’s role in MSCs’ potency and offering a novel approach by modulating the SL pathway to enhance MSC pro- regenerative properties. This can lead to high-quality, therapeutic MSC cell therapies and improved MSC characterization techniques.