Bioreactors expansion of human mesenchymal stromal cell therapies: platforms, parameters, challenges and opportunities.

Human mesenchymal stromal cells (MSC) have garnered significant interest as cell therapy for a multitude of indications. Despite their clinical potential, the development and commercialization of MSC-based products have been hampered by the challenge in scalable production of MSC ex vivo. At present, bioreactor expansion represents the most significant technical hurdle during the MSC manufacturing process. Intrinsic properties of MSCs, e.g. cell senescence, donor heterogeneity, and shear stress-sensitivity lead to suboptimal productivity and inconsistent quality, that often confounded the clinical efficacy readout. Herein we review the key aspects in bioreactor cultivation of MSCs, including the instrument platforms, critical process parameters, process scale-up, downstream and analytics. Cell senescence, the key limitation in ex vivo MSC expansion, was also discussed along with emerging strategies to circumvent the obstacle. Technological improvement and mechanistic understanding of MSC expansion in bioreactors will accelerate the clinical development of MSC as regenerative medicine.