title: Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles.
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 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.
authors: Scottish Centre for Regenerative Medicine, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors: Bruna
authors: B
authors: Corradetti
authors: Paz
authors: P
authors: Freile
authors: Steve
authors: S
authors: Pells
authors: Pierre
authors: P
authors: Bagnaninchi
authors: Jason
authors: J
authors: Park
authors: Tarek M
authors: TM
authors: Fahmy
authors: Paul A
authors: PA
authors: de Sousa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001360:Avidin / Q000737:chemistry; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects*; D005434:Flow Cytometry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology*; D016256:Lewis X Antigen / Q000737:chemistry / Q000276:immunology; D008081:Liposomes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D019899:Paracrine Communication / Q000187:drug effects; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000911:Antibodies, Monoclonal; D036341:Intercellular Signaling Peptides and Proteins; D053605:Leukemia Inhibitory Factor; D016256:Lewis X Antigen; C507838:Lif protein, mouse; D008081:Liposomes; D001360:Avidin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid