The translation of stem cells into viable regenerative and diagnostic technologies is dependent on reproducible techniques to produce defined cell populations with high yields. Our work aims to develop novel tools and technologies that are capable of being directly integrated into bioprocessing systems.
Scale-up Technologies - Most industrial bioprocessing relies upon suspension bioreactors, and pluripotent stem cells have been successfully cultured in suspension as aggregates, on microcarriers, or encapsulated within hydrogel materials. We have developed bench scale culture platforms that recapitulate aspects of fluid mixing in standard bioprocess platforms. The physical protection afforded by encapsulation prevents agglomeration, while simultaneously protecting the stem cells from the damage and influence of hydrodynamic forces. Ultimately, advances in scale-up technologies will enable the development of engineered microtissues while simultaneously considering scalability issues.
Controlled Differentiation Platforms - To produce homogeneous cell populations in large numbers, it is necessary to efficiently promote differentiation toward the desired lineage. We have made advancements in controlled differentiation of pluripotent stem cells toward the mesodermal lineages, specifically cardiac, bone, and cartilage, through the application of hydrodynamic forces (shear forces and changes in transport), by incorporating microparticles with specific stimuli, and through soluble factor delivery.
Monitoring & Separation Processes - An important consideration in bioprocess design is the integration of on-line technologies for downstream processing and quality control to achieve robust and reproducible cell yields with defined phenotypes at large scales. Additionally, the product(s) of interest, whether a differentiated cell population or a collection of trophic factors, must be purified from the remaining components. To progress in these areas, we have developed microfluidic technologies for separating pluripotent populations from the surrounding differentiated cells, either to select for bona fide iPSCs or for differentiated progeny.