Quality Manufacturing of Mesenchymal Stem/Stromal Cells Using Scalable and Controllable Bioreactor Platforms

This publication reviews the scientific and engineering considerations required to manufacture human mesenchymal stem/stromal cells (hMSCs) at clinically and commercially relevant scales. The authors discuss upstream process development, including media selection, culture substrates, microcarriers, and scalable bioreactor technologies suitable for adherent cell expansion. Multiple platform types are evaluated, including hollow-fiber, fixed-bed, stirred-tank, and Vertical-Wheel bioreactors. The chapter examines process optimization strategies, critical quality attributes, critical process parameters, hydrodynamics, harvest efficiency, and scale-down modeling. Special emphasis is placed on establishing robust, reproducible, and GMP-compatible manufacturing systems capable of generating high cell yields while maintaining phenotypic and functional characteristics. The publication serves as a comprehensive overview of bioprocess-development principles for large-scale hMSC manufacturing.