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

Dixon, James E. and Shah, Disheet A. and Rogers, Catherine and Hall, Stephen and Weston, Nicola and Parmenter, Christopher D. J. and McNally, Donal and 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

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Abstract

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.

Item Type: Article
Keywords: Human Embryonic Stem Cells, Differentiation, Hydrogel, Cardiomyocyte
Schools/Departments: University of Nottingham, UK > Faculty of Engineering > Department of Mechanical, Materials and Manufacturing Engineering
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: https://doi.org/10.1073/pnas.1319685111
Depositing User: Eprints, Support
Date Deposited: 12 Jan 2018 12:05
Last Modified: 02 Jul 2018 09:17
URI: http://eprints.nottingham.ac.uk/id/eprint/49049

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