(73a) Engineering Thermoresponsive Biomaterials for Investigating and Controlling Human Embryonic Stem Cell Function

Human pluripotent stem cells including embryonic stem cells (hESCs) offer major potential as an unlimited source of functional cells for a range of biomedical applications; however, the development of large scale cell manufacturing systems to enable this potential faces many challenges. For example, expanding and differentiating hESCs to produce sufficient numbers of midbrain dopaminergic neurons to treat Parkinson’s Disease, medium spiny neurons to treat Huntington’s Disease, or beta cells to treat diabetes will require 10s-1000s of football fields of surface area using conventional 2D culture systems. In addition, 2D systems use poorly-defined human and animal tissue derived components. We have designed and synthesized tunable thermoresponsive biomaterials that enable fully-defined, 3D culture systems for scalable hESC expansion and differentiation into many lineages to enable cell replacement therapies. For example, medium spiny neurons generated in 3D exhibited high viability upon implantation into mouse striatum and led to functional improvement in a model of Huntington’s Disease. Furthermore, this 3D system in combination with novel optogenetic technologies has enabled the formation of hESC-based organoids as models to study early stages of human development, including gastrulation and neural tube formation. A defined and scalable cell culture platform can thus generate high quality differentiated cells and cultures and thereby accelerate both basic and translational research.