| Summary: | The ability of materials to define the architecture and micro-environment experienced by cells provides new opportunities to direct the fate of human pluripotent stem cells (HPSCs) (Robinton DA, et al (2012) Nature 81:295-305). However, the conditions required for self-renewal verses differentiation of HPSCs are different and a single system that efficiently achieves both outcomes is not available (Giobbe GG, et al. (2012) Biotech Bioeng 109:3119 - 3132). We have addressed this dual need by developing a hydrogel - based material that uses ionic decrosslinking to remove a self-renewal permissive hydrogel (alginate) and switch to a differentiation-permissive micro-environment (collagen). Adjusting the timing of this switch can preferentially steer the HPSC differentiation to mimic lineage commitment during gastrulation to ectoderm (early switch) or mesoderm/endoderm (late switch). As an exemplar differentiated cell type, we showed that directing early-lineage specification using this single system can promote cardiogenesis with increased gene expression in high-density cell populations. This work will facilitate regenerative medicine by allowing in situ HPSC expansion to be coupled with early lineage-specification within defined tissue geometries.
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