Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles

Bruna Corradetti, Paz Freile, Steve Pells, Pierre Bagnaninchi, Jason Park, Tarek M. Fahmy, Paul A. de Sousa

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Stem cell growth and differentiation is controlled by intrinsic and extrinsic factors. The latter includes growth factors, which are conventionally supplied in vitro in media exchanged daily. Here, we illustrate the use of affinity targeted biodegradable nanoparticles to mediate paracrine stimulation as an alternative approach to sustain the growth and pluripotency of mouse embryonic stem cells. Leukaemia Inhibitory Factor (LIF) was encapsulated in biodegradable nanoparticles and targeted to the cell surface using an antibody to the oligosaccharide antigen SSEA-1. Sustained release of LIF from nanoparticles composed of a solid Poly(lactide-co-glycolic acid) polyester or a hydrogel-based liposomal system, we term Nanolipogel, replenished once after each cell passage, proved as effective as daily replenishment with soluble LIF for maintenance of pluripotency after 5 passages using 104-fold less LIF. Our study constitutes an alternative paradigm for stem cell culture, providing dynamic microenvironmental control of extrinsic bioactive factors benefiting stem cell manufacturing.

Original languageEnglish (US)
Pages (from-to)6634-6643
Number of pages10
JournalBiomaterials
Volume33
Issue number28
DOIs
StatePublished - Oct 2012

Keywords

  • Biodegradable nanoparticles
  • Embryonic stem cell
  • Paracrine delivery
  • Renewal

ASJC Scopus subject areas

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

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