Research Focus: Lipidomic Characterization of Mesenchymal Stromal Cells for Critical Quality Attributes.

Cell therapies are expected to increase over the next decade due to increasing demand for clinical applications. In particular, mesenchymal stromal cells (MSCs) have gained much interest due to MSCs’ multipotent differentiation, immunomodulation, immune suppression, and pro-regenerative properties via secreted cytokines, extracellular vesicles (EVs) and trophic factors. Despite their therapeutic potential, discrepancies in MSC characterization have limited further clinical application, resulting in lessened therapeutic capacity once in vivo. This calls for additional needs for cell characterization such as multi-omic profiling.

Lipidomics, a sub-branch of metabolomics, is a powerful technique that combines high-throughput analytical methods and informatics to quantify and characterize cells’ lipid profile to describe complex cellular metabolism. Sphingolipids, a class of bioactive lipids, have shown to be involved in unique functional roles in cell biology. Our work focuses on characterizing MSCs sphingolipidome for critical quality attributes to better understand sphingolipid’s role in MSC therapeutic efficacy. Additionally, we aim to uncover how introducing perturbations to the sphingolipid pathway can enhance MSC quality.

Relevant Publications:

• Priyanka P., DeVeaux S., Leitmann B., Rui K., Botchwey EA, Mortensen, LJ. Understanding Mesenchymal Stem Cell Immune Potency: A Morpholomic and Lipidomic Perspective. BioRxiv. May 2022
• DeVeaux SA, Ogle ME, Vyshnya S, Chiappa NF, Leitmann B, Rudy R, Day A, Mortensen LJ, Kurtzberg J, Roy K, Botchwey EA. Characterizing Human Mesenchymal Stromal Cells Immune Modulatory Potency Using Targeted Lipidomic Profiling of Sphingolipids. Cytotherapy. February 2022.