Melissa Kinney

For the therapeutic promise of embryonic stem cells (ESCs) to be fully realized, scalable approaches to efficiently direct differentiation must be developed.  Directed differentiation methods often rely on the addition of morphogens to monolayer cultures of ESCs, which permits homogeneous delivery; however, this culture format is not easily amenable to the production of increased yields of differentiated cells necessary for therapeutic applications.  Although suspension culture of ESCs as 3D multicellular aggregates is scalable, morphogen delivery is often constrained to the exterior cells due to diffusive transport limitations.  The proposed work aims to develop an enabling technology which will allow more precise control of parameters affecting ESC differentiation, such as temporal kinetics and spatial localization of morphogen delivery.  Ultimately, understanding the impact of environmental perturbations, such as fluid dynamic parameters, on stem cell expansion and differentiation motivates the rational design of bioreactors and bioprocessing systems for tissue engineering applications.  The outcomes of this work are expected to yield insights regarding the transport requirements and limitations in 3D tissues, which will create new opportunities for the scalable culture of multicellular assemblies and large tissue constructs for applications in tissue engineering and regenerative medicine.