Biological considerations in stem cell manufacturing

Background: Cell-based therapeutics have made advances in recent years. One of the most clinically studied products in regenerative medicine is mesenchymal stromal cells (MSCs). MSCs have stem cell-like properties and the ability to modulate immune cell function, making them valuable for the treatment of a wide array of inflammatory and degenerative disease conditions. However, MSC therapy requires large numbers of cells to be generated via scale-up manufacturing methods (e.g. propagation on microcarriers in stirred-tank bioreactors). Such manufacturing methods are not tailored for MSC expansion and may alter their biological function and, consequently, clinical effectiveness. The successful translation of cell therapy to the clinic requires an understanding of how up-scaling therapeutic cell production affects their biological properties and immunomodulatory function. Project aim/s: The project aims to investigate changes in the biological function of MSCs generated from commercial scale-up processes (e.g. on microcarriers in bioreactors), compared to conventional planar culture systems. Techniques: This project will utilise techniques applicable to stem cells, immunology and biomanufacturing: 2D and 3D cell culture, bioreactor systems, flow cytometry, immunoassays, stem cell differentiation, fluorescence microscopy. Reference: Cherian D, Bhuvan T, Meagher L, Heng TSP (2020). Biological Considerations in Scaling Up Therapeutic Cell Manufacturing. Frontiers in Pharmacology 11:654. doi: 10.3389/fphar.2020.00654.