Novel impeller design for stem cell bioprocessing and its application in hMSC stirred-tank bioreactor cultures

Please click Additional Files below to see the full abstract

Engineering Characterisation of the Bach Impeller and its Application to Mesenchymal Stem Cell Microcarrier Cultures

Treating complex chronic diseases with stem cells offers great promise in regenerative medicine. However, large quantities of cells are required, and the need for manufacturing platforms that can supply clinically relevant doses is therefore increasing. Encouraging results have been reported using stirred-tank bioreactors (STRs), where human Mesenchymal Stem Cells (hMSCs) are cultured while adherent to microcarriers. Because STRs can be volumetrically scaled-up, their use may offer increased cost-efficiency. Within the STR, the impeller geometry and design are critical to the efficiency of suspension, mixing, and mass transfer. The thesis describes the experimental characterisation of the flow produced by a novel impeller, called the Bach impeller, and its use to inform biological experiments to achieve higher productivity in the manufacturing of hMSCs. Novel impeller designs with increased fluid flow control and reduced power input may be required to ensure greater consistency in growing shear-sensitive cells. Most studies were historically focused on standard impeller geometries from chemical engineering applications, while recently, it has become increasingly apparent that mixing has a key role in controlling biological culture environments. Adopting a multi-disciplinary approach is crucial to propose tailored bioprocessing solutions to manufacture future cell therapies. Several experimental techniques were used in a bioreactor mimic to measure key impeller characteristics such as mixing time, suspension speed, impeller power input, oxygen mass transfer, or fluid flow velocities. The engineering experiments showed that the impeller represents an efficient mixing device that suspends particles in fluids at low power inputs. Subsequent biological cell cultures performed with the novel impeller system showed faster cell growth than conventional Spinner flask solutions. In addition, the engineering data supported the scaling to a 5 L reactor without relying on trial-and-error approaches. Importantly, the hMSCs retained critical quality attributes such as immunophenotype and multipotency