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
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Medientyp:
E-Artikel
Titel:
Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation
Beteiligte:
Dixon, James E.;
Shah, Disheet A.;
Rogers, Catherine;
Hall, Stephen;
Weston, Nicola;
Parmenter, Christopher D. J.;
McNally, Donal;
Denning, Chris;
Shakesheff, Kevin M.
Erschienen:
National Academy of Sciences, 2014
Erschienen in:Proceedings of the National Academy of Sciences of the United States of America
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>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.</p>