Bioreactors and Downstream Processing for Stem Cell Manufacturing

Abstract Manufacture of stem cells at a scale and at a cost that is commercially viable while retaining the desired product quality is a major challenge in the emerging field of cellular therapy. Single-use bioreactor culture using suspended microcarriers that provides more surface area per volume with a more consistent and controlled growth environment than that of many individual flasks or roller bottles is considered a promising option. However, the conventional bioreactor technology developed for proteins and virus production from suspended individual cells should be reengineered to satisfy the unique growth characteristics of anchorage-dependent primary cells on the surface of microcarriers as well as to provide efficient fluid dynamics for uniform suspension of the microcarriers. A novel single-use, vertical-wheel bioreactor platform that provides adequate mixing and homogeneous microcarrier suspension across a wide range of working volumes with low shear stress and low power inputs is evaluated through physical test, computational fluid dynamics analysis, and biological experiment in order to address the specialized manufacturing requirements for stem cells and cellular therapy products. The economies of scale associated with using large bioreactors to produce cellular products will undoubtedly enable a new industry that uses cells to treat many currently unmet medical needs.