S'Dravious DeVeaux
BME PhD Proposal Presentation

Date: 2022-10-18
Time: 9:00 - 11:00
Location / Meeting Link: Krone Engineered Biosystems Building Children's Healthcare of Atlanta Seminar Room (EBB CHOA) / https://gatech.zoom.us/j/3585647664?pwd=Z0thTlJRSEFuWlVxdXFRZUNSQk1ydz09

Committee Members:
Edward Botchwey, PhD (Advisor); Krishnendu Roy, PhD (Co-Advisor); Sakis Mantalaris, PhD; Carolyn Yeago, PhD; Facundo Fernández, PhD; Aditi Das, PhD


Title: Assessing Therapeutic Potency of Mesenchymal Stromal Cells by Targeted Lipidomic 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 critical 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 to better explain MSC’s therapeutic potency. Lipidomics is an analytical tool that 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. Bioactive lipids, such as sphingolipids (SLs), participate in cell signaling processes that are essential to various cell functions and maintaining homeostasis. However, their role in MSC behavior and therapeutic potency remains largely unknown. The objective of this work is to understand how bioactive SLs are involved in MSC immunomodulation and tissue regenerative properties. In Aim 1, liquid chromatography-tandem mass spectrometry will be utilized to target and assess MSC bioactive SLs from 1) multiple tissue sources and 2) MSCs treated with an inflammatory cytokine in order to stimulate their immunomodulatory properties. In Aim 2, the SL metabolic network will be modulated by exogenous SL enzymes and MSC hydrogel encapsulation to assess the SL metabolic changes and their therapeutic potency. Overall, this work will develop an understanding of SL’s role in MSCs’ therapeutic potency by characterizing MSCs by their bioactive SL profile and offering a novel approach by modulating the SL pathway to enhance MSC immunomodulatory and tissue regenerative properties. This proposed project may lead to high-quality, therapeutic MSC cell therapies and improved MSC characterization techniques.