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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

Kevin M. Shakesheff



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.

Citation

Dixon, J. E., Shah, D. A., Rogers, C., Hall, S., Weston, N., Parmenter, C. D., …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), 5580-5585. https://doi.org/10.1073/pnas.1319685111

Journal Article Type Article
Acceptance Date Mar 4, 2014
Online Publication Date Mar 27, 2014
Publication Date Apr 15, 2014
Deposit Date Jan 12, 2018
Publicly Available Date Jan 12, 2018
Journal Proceedings of the National Academy of Sciences of the United States of America
Print ISSN 0027-8424
Electronic ISSN 1091-6490
Publisher National Academy of Sciences
Peer Reviewed Peer Reviewed
Volume 111
Issue 15
Pages 5580-5585
DOI https://doi.org/10.1073/pnas.1319685111
Keywords Human embryonic stem cells, Differentiation, Hydrogel, Cardiomyocyte
Public URL http://eprints.nottingham.ac.uk/id/eprint/49049
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.nottingham.ac.uk/end_user_agreement.pdf

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Dixon et al. PNAS 2014 ePrints.pdf (835 Kb)
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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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