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

Dixon, James E.; Shah, Disheet A.; Rogers, Catherine; Hall, Stephen; Weston, Nicola; Parmenter, Christopher D.J.; McNally, Donal; Denning, Chris; Shakesheff, Kevin M.

Authors

Disheet A. Shah

Catherine Rogers

Stephen Hall

Nicola Weston

CHRIS DENNING chris.denning@nottingham.ac.uk
Professor of Stem Cell Biology



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.

Journal Article Type Article
Publication Date Apr 15, 2014
Journal Proceedings of the National Academy of Sciences
Electronic ISSN 1091-6490
Publisher National Academy of Sciences
Peer Reviewed Peer Reviewed
Volume 111
Issue 15
Pages 5580-5585
APA6 Citation Dixon, J. E., Shah, D. A., & Rogers, C. (2014). Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation. Proceedings of the National Academy of Sciences, 111(15), 5580-5585. doi:10.1073/pnas.1319685111
DOI https://doi.org/10.1073/pnas.1319685111
Keywords Human embryonic stem cells, Differentiation, Hydrogel, Cardiomyocyte
Publisher URL http://www.pnas.org/content/111/15/5580
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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