Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation.
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.
Wolfson Centre for Stem Cells, Tissue Engineering, and Modelling, Centre of Biomolecular Sciences, School of Pharmacy, Medical Engineering Unit, School of Mechanical, Materials and Manufacturing Engineering, Nottingham Nanotechnology and Nanoscience Centre, Faculty of Engineering, and School of Medicine, University of Nottingham, Nottingham NG7 2RD, United Kingdom.
James E
JE
Dixon
Disheet A
DA
Shah
Catherine
C
Rogers
Stephen
S
Hall
Nicola
N
Weston
Christopher D J
CD
Parmenter
Donal
D
McNally
Chris
C
Denning
Kevin M
KM
Shakesheff
D000464:Alginates; D002232:Carbocyanines; D002454:Cell Differentiation / Q000187:drug effects*; D003094:Collagen; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology*; D044968:Regenerative Medicine / Q000379:methods; D013057:Spectrum Analysis; D055153:Stem Cell Niche / Q000187:drug effects*
D000464:Alginates; D002232:Carbocyanines; D006603:Hexuronic Acids; D020100:Hydrogels; C024286:3,3'-dioctadecylindocarbocyanine; D020723:Glucuronic Acid; D003094:Collagen
cardiomyocyte; human embryonic stem cells