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

TitleParacrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles.
Publication TypeJournal Article
Year of Publication2012
AuthorsCorradetti B, Freile P, Pells S, Bagnaninchi PO, Park J, Fahmy TM, De Sousa PA
Date Published2012 Oct
KeywordsAnimals, Antibodies, Monoclonal, Antigens, CD15, Avidin, Cell Culture Techniques, Cell Differentiation, Cell Proliferation, Embryonic Stem Cells, Flow Cytometry, Hydrogel, Intercellular Signaling Peptides and Proteins, Lactic Acid, Leukemia Inhibitory Factor, Liposomes, Mice, Microscopy, Electron, Scanning, Nanoparticles, Paracrine Communication, Particle Size, Polyglycolic Acid

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.

Alternate JournalBiomaterials
PubMed ID22749449
Grant ListBB/G010374/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
G0300484 / / Medical Research Council / United Kingdom
U19A1082713-04 / / PHS HHS / United States
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