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.

DOI: https://doi.org/10.1073/pnas.1319685111

Abstract

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.