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

Biomaterials. 2012 Oct;33(28):6634-43. doi: 10.1016/j.biomaterials.2012.06.011. Epub 2012 Jun 30.


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 10(4)-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Avidin / chemistry
  • Cell Culture Techniques / methods*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Embryonic Stem Cells / drug effects*
  • Flow Cytometry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Lactic Acid / chemistry
  • Lactic Acid / metabolism
  • Leukemia Inhibitory Factor / pharmacology*
  • Lewis X Antigen / chemistry
  • Lewis X Antigen / immunology
  • Liposomes / chemistry
  • Liposomes / immunology
  • Liposomes / metabolism*
  • Mice
  • Microscopy, Electron, Scanning
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Paracrine Communication / drug effects
  • Particle Size
  • Polyglycolic Acid / chemistry
  • Polyglycolic Acid / metabolism
  • Polylactic Acid-Polyglycolic Acid Copolymer


  • Antibodies, Monoclonal
  • Intercellular Signaling Peptides and Proteins
  • Leukemia Inhibitory Factor
  • Lewis X Antigen
  • Lif protein, mouse
  • Liposomes
  • Avidin
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyglycolic Acid
  • Lactic Acid