Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation

Dixon, J. E.; Shah, D. A.; Rogers, C.; Hall, S.; Weston, N.; Parmenter, C. D. J.; McNally, D.; Denning, C. and Shakesheff, K. M. (2014). Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation. Proceedings of the National Academy of Sciences, 111(15) pp. 5580–5585.



The ability of materials to define the architecture and microenvironment experienced by cells provides new opportunities to direct the fate of human pluripotent stem cells (HPSCs) [Robinton DA, Daley GQ (2012) Nature 481(7381):295–305]. However, the conditions required for self-renewal vs. differentiation of HPSCs are different, and a single system that efficiently achieves both outcomes is not available [Giobbe GG, et al. (2012) Biotechnol Bioeng 109(12):3119–3132]. We have addressed this dual need by developing a hydrogel-based material that uses ionic de-cross-linking to remove a self-renewal permissive hydrogel (alginate) and switch to a differentiation-permissive microenvironment (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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