Microencapsulation of embryonic and mesenchymal stem cells for scalable bioprocessing

Stem cells hold tremendous promise as tools for regenerative medicine and drug discovery. Embryonic stem cells (ESCs) are pluripotent, signifying that they have the ability to differentiate into all adult cell types, while mesenchymal stem cells (MSCs) are multipotent and are more limited in their differentiation capacity. Despite the great promise of stem cells, there are many challenges to overcome before stem cell-derived therapies can be made broadly available, including the lack of processes to manufacture viable and homogenous cell populations. Currently, the industrial production of mammalian cells occurs in large scale bioreactors, which impart hydrodynamic forces that can damage stem cells and influence their differentiation. Stem cells are very sensitive to environmental stimuli, as external signals in the culture environment provide cues that determine whether stem cells continue to self-renew or whether they differentiate into a specific cell type. Current bioprocesses also require that stem cells, which are normally adherent, be cultured in suspension in order to achieve higher cell densities. One possible solution to these challenges is to encapsulate stem cells in hydrogels, such as alginate beads. Encapsulation protects cells from hydrodynamic shear forces found in the reactor environment, prevents agglomeration of stem cell aggregates, and allows for diffusion of nutrients and oxygen through the encapsulation material. Encapsulation may also be used to modulate cellular phenotype. Therefore, the goal of this study is to examine the impact of alginate microencapsulation on the viability and phenotype of ESC and MSC populations.