Long-term maintenance of mouse embryonic stem cell pluripotency by manipulating integrin signaling within 3D scaffolds without active Stat3

Seung Tae Lee, Jung Im Yun, Andre J. van der Vlies, Stephan Kontos, Mi Jang, Seung Pyo Gong, Dae Yong Kim, Jeong M. Lim, Jeffrey A. Hubbell

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

We engineered an acellular biomimetic microenvironment to regulate stem cell fate and applied it to maintain mouse embryonic stem (ES) cell self-renewal. In the 3D environment formed using hydrogel scaffolds in which specific integrin ligation was provided, Stat3 activation by exogenous leukemia inhibitory factor (LIF) no longer acted as a limiting factor for stem cell self-renewal. Instead, simultaneous stimulation of integrins α5β1, αvβ5, α6β1 and α9β1 within the 3D scaffold greatly increased Akt1 and Smad 1/5/8 activation, which resulted in prolonged self-renewal of the ES cells. The ES cells exposed to the combined stimulation of the integrins for 4 wk in LIF-free 3D scaffolds maintained the spherical morphology of cell colonies without losing any activity of pluripotency. In conclusion, cell niche-specific integrin signaling within the 3D environment supported mouse ES cell self-renewal, and the resulting integrin signaling replaced Stat3 with Akt1 and Smad 1/5/8 as critical signals for mouse ES cell self-renewal.

Original languageEnglish (US)
Pages (from-to)8934-8942
Number of pages9
JournalBiomaterials
Volume33
Issue number35
DOIs
StatePublished - Dec 2012

Keywords

  • Embryonic stem cell
  • Hydrogel
  • Integrin
  • Niche
  • Self-renewal
  • Signaling

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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