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

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...

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Main Authors: Dixon, James E., Shah, Disheet A., Rogers, Catherine, Hall, Stephen, Weston, Nicola, Parmenter, Christopher D. J., McNally, Donal, Denning, Chris, Shakesheff, Kevin M.
Format: Article
Language:English
Published: National Academy of Sciences 2014
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Online Access:https://eprints.nottingham.ac.uk/49049/
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author Dixon, James E.
Shah, Disheet A.
Rogers, Catherine
Hall, Stephen
Weston, Nicola
Parmenter, Christopher D. J.
McNally, Donal
Denning, Chris
Shakesheff, Kevin M.
author_facet Dixon, James E.
Shah, Disheet A.
Rogers, Catherine
Hall, Stephen
Weston, Nicola
Parmenter, Christopher D. J.
McNally, Donal
Denning, Chris
Shakesheff, Kevin M.
author_sort Dixon, James E.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-490492020-05-08T09:30:20Z https://eprints.nottingham.ac.uk/49049/ 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. 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. National Academy of Sciences 2014-04-15 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/49049/1/Dixon%20et%20al.%20PNAS%202014%20ePrints.pdf 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 Human Embryonic Stem Cells Differentiation Hydrogel Cardiomyocyte http://www.pnas.org/content/111/15/5580 doi:10.1073/pnas.1319685111 doi:10.1073/pnas.1319685111
spellingShingle Human Embryonic Stem Cells
Differentiation
Hydrogel
Cardiomyocyte
Dixon, James E.
Shah, Disheet A.
Rogers, Catherine
Hall, Stephen
Weston, Nicola
Parmenter, Christopher D. J.
McNally, Donal
Denning, Chris
Shakesheff, Kevin M.
Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
title Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
title_full Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
title_fullStr Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
title_full_unstemmed Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
title_short Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
title_sort combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
topic Human Embryonic Stem Cells
Differentiation
Hydrogel
Cardiomyocyte
url https://eprints.nottingham.ac.uk/49049/
https://eprints.nottingham.ac.uk/49049/
https://eprints.nottingham.ac.uk/49049/