Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiationTools Dixon, James E., Shah, Disheet A., Rogers, Catherine, Hall, Stephen, Weston, Nicola, Parmenter, Christopher D. J., McNally, Donal, Denning, Chris and Shakesheff, Kevin 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. ISSN 1091-6490
Official URL: http://www.pnas.org/content/111/15/5580
AbstractThe 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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